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Genetic Aberrations Associated with Photodynamic Therapy in Colorectal Cancer Cells

Identifieur interne : 000742 ( Pmc/Checkpoint ); précédent : 000741; suivant : 000743

Genetic Aberrations Associated with Photodynamic Therapy in Colorectal Cancer Cells

Auteurs : Heidi Abrahamse ; Nicolette Nadene Houreld

Source :

RBID : PMC:6651415

Abstract

Photodynamic therapy (PDT) is a cancer treatment modality that utilizes three components: light (λ 650–750 nm), a photosensitizer (PS) and molecular oxygen, which upon activation renders the modality effective. Colorectal cancer has one of the highest incident rates as well as a high mortality rate worldwide. In this study, a zinc (Zn) metal-based phthalocyanine (ZnPcSmix) PS was used to determine its efficacy for the treatment of colon adenocarcinoma cells (DLD-1 and Caco-2). Photoactivation of the PS was achieved by laser irradiation at a wavelength of 680 nm. Dose responses were performed to establish optimal PS concentration and irradiation fluence. A working combination of 20 µM ZnPcSmix and 5 J/cm2 was used. Biochemical responses were determined after 1 or 24 h incubation post-treatment. Since ZnPcSmix is localized in lysosomes and mitochondria, mitochondrial destabilization analysis was performed monitoring mitochondrial membrane potential (MMP). Cytosolic acidification was determined measuring hydrogen peroxide (H2O2) levels in the cytoplasm. Having established apoptotic cell death induction, an apoptosis PCR array was performed to establish the apoptotic mechanism. In DLD-1 cells, expression of genes included 3 up-regulated and 20 down-regulated genes while in Caco-2 cells, there were 16 up-regulated and 22 down-regulated genes. In both cell lines, in up-regulated genes, there was a combination of pro- and anti-apoptotic genes that were significantly expressed. Gene expression results showed that more tumorigenic cells (DLD-1) went through apoptosis; however, they exhibit increased risk of resistance and recurrence, while less tumorigenic Caco-2 cells responded better to PDT, thus being suggestive of a better prognosis post-PDT treatment. In addition, the possible apoptotic mechanisms of cell death were deduced based on the genetic expression profiling of regulatory apoptotic inducing factors.


Url:
DOI: 10.3390/ijms20133254
PubMed: 31269724
PubMed Central: 6651415


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PMC:6651415

Le document en format XML

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<p>Photodynamic therapy (PDT) is a cancer treatment modality that utilizes three components: light (λ 650–750 nm), a photosensitizer (PS) and molecular oxygen, which upon activation renders the modality effective. Colorectal cancer has one of the highest incident rates as well as a high mortality rate worldwide. In this study, a zinc (Zn) metal-based phthalocyanine (ZnPcSmix) PS was used to determine its efficacy for the treatment of colon adenocarcinoma cells (DLD-1 and Caco-2). Photoactivation of the PS was achieved by laser irradiation at a wavelength of 680 nm. Dose responses were performed to establish optimal PS concentration and irradiation fluence. A working combination of 20 µM ZnPcSmix and 5 J/cm
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<pmc article-type="research-article">
<pmc-dir>properties open_access</pmc-dir>
<front>
<journal-meta>
<journal-id journal-id-type="nlm-ta">Int J Mol Sci</journal-id>
<journal-id journal-id-type="iso-abbrev">Int J Mol Sci</journal-id>
<journal-id journal-id-type="publisher-id">ijms</journal-id>
<journal-title-group>
<journal-title>International Journal of Molecular Sciences</journal-title>
</journal-title-group>
<issn pub-type="epub">1422-0067</issn>
<publisher>
<publisher-name>MDPI</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="pmid">31269724</article-id>
<article-id pub-id-type="pmc">6651415</article-id>
<article-id pub-id-type="doi">10.3390/ijms20133254</article-id>
<article-id pub-id-type="publisher-id">ijms-20-03254</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Article</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>Genetic Aberrations Associated with Photodynamic Therapy in Colorectal Cancer Cells</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<contrib-id contrib-id-type="orcid" authenticated="true">https://orcid.org/0000-0001-5002-827X</contrib-id>
<name>
<surname>Abrahamse</surname>
<given-names>Heidi</given-names>
</name>
<xref rid="c1-ijms-20-03254" ref-type="corresp">*</xref>
</contrib>
<contrib contrib-type="author">
<contrib-id contrib-id-type="orcid" authenticated="true">https://orcid.org/0000-0002-1515-8260</contrib-id>
<name>
<surname>Houreld</surname>
<given-names>Nicolette Nadene</given-names>
</name>
</contrib>
</contrib-group>
<aff id="af1-ijms-20-03254">Laser Research Centre, Faculty of Health Sciences, University of Johannesburg, Johannesburg 2028, South Africa</aff>
<author-notes>
<corresp id="c1-ijms-20-03254">
<label>*</label>
Correspondence:
<email>habrahamse@uj.ac.za</email>
</corresp>
</author-notes>
<pub-date pub-type="epub">
<day>02</day>
<month>7</month>
<year>2019</year>
</pub-date>
<pub-date pub-type="collection">
<month>7</month>
<year>2019</year>
</pub-date>
<volume>20</volume>
<issue>13</issue>
<elocation-id>3254</elocation-id>
<history>
<date date-type="received">
<day>21</day>
<month>5</month>
<year>2019</year>
</date>
<date date-type="accepted">
<day>11</day>
<month>6</month>
<year>2019</year>
</date>
</history>
<permissions>
<copyright-statement>© 2019 by the authors.</copyright-statement>
<copyright-year>2019</copyright-year>
<license license-type="open-access">
<license-p>Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (
<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">http://creativecommons.org/licenses/by/4.0/</ext-link>
).</license-p>
</license>
</permissions>
<abstract>
<p>Photodynamic therapy (PDT) is a cancer treatment modality that utilizes three components: light (λ 650–750 nm), a photosensitizer (PS) and molecular oxygen, which upon activation renders the modality effective. Colorectal cancer has one of the highest incident rates as well as a high mortality rate worldwide. In this study, a zinc (Zn) metal-based phthalocyanine (ZnPcSmix) PS was used to determine its efficacy for the treatment of colon adenocarcinoma cells (DLD-1 and Caco-2). Photoactivation of the PS was achieved by laser irradiation at a wavelength of 680 nm. Dose responses were performed to establish optimal PS concentration and irradiation fluence. A working combination of 20 µM ZnPcSmix and 5 J/cm
<sup>2</sup>
was used. Biochemical responses were determined after 1 or 24 h incubation post-treatment. Since ZnPcSmix is localized in lysosomes and mitochondria, mitochondrial destabilization analysis was performed monitoring mitochondrial membrane potential (MMP). Cytosolic acidification was determined measuring hydrogen peroxide (H
<sub>2</sub>
O
<sub>2</sub>
) levels in the cytoplasm. Having established apoptotic cell death induction, an apoptosis PCR array was performed to establish the apoptotic mechanism. In DLD-1 cells, expression of genes included 3 up-regulated and 20 down-regulated genes while in Caco-2 cells, there were 16 up-regulated and 22 down-regulated genes. In both cell lines, in up-regulated genes, there was a combination of pro- and anti-apoptotic genes that were significantly expressed. Gene expression results showed that more tumorigenic cells (DLD-1) went through apoptosis; however, they exhibit increased risk of resistance and recurrence, while less tumorigenic Caco-2 cells responded better to PDT, thus being suggestive of a better prognosis post-PDT treatment. In addition, the possible apoptotic mechanisms of cell death were deduced based on the genetic expression profiling of regulatory apoptotic inducing factors.</p>
</abstract>
<kwd-group>
<kwd>photodynamic therapy</kwd>
<kwd>colorectal cancer</kwd>
<kwd>zinc phthalocyanine</kwd>
<kwd>apoptotic pathway</kwd>
</kwd-group>
</article-meta>
</front>
<floats-group>
<fig id="ijms-20-03254-f001" orientation="portrait" position="float">
<label>Figure 1</label>
<caption>
<p>Hydrogen peroxide (H
<sub>2</sub>
O
<sub>2</sub>
) was determined after 1 and 24 h post-treatment and relative fluorescence units were measured (530Ex/590Em). Significant differences as compared to untreated control cells is shown as *
<italic>p</italic>
< 0.05, **
<italic>p</italic>
< 0.01 and ***
<italic>p</italic>
< 0.001. There were significantly increased H
<sub>2</sub>
O
<sub>2</sub>
levels in PDT treated DLD-1 and Caco-2 cells after both 1 and 24 h incubation.</p>
</caption>
<graphic xlink:href="ijms-20-03254-g001"></graphic>
</fig>
<fig id="ijms-20-03254-f002" orientation="portrait" position="float">
<label>Figure 2</label>
<caption>
<p>Loss of mitochondrial membrane potential in DLD-1 cells was analyzed 1 or 24 h post-treatment by JC-1 staining using flow cytometry. Significant differences as compared to untreated cells as shown as ***
<italic>p</italic>
< 0.001. After 1 h incubation there was an increase in depolarized PDT cells compared to all control cells, which increased significantly after 24 h.</p>
</caption>
<graphic xlink:href="ijms-20-03254-g002"></graphic>
</fig>
<fig id="ijms-20-03254-f003" orientation="portrait" position="float">
<label>Figure 3</label>
<caption>
<p>Loss of mitochondrial membrane potential in Caco-2 cells was analyzed 1 or 24 h post-treatment by JC-1 staining using flow cytometry. Significant differences as compared to untreated cells as shown as ***
<italic>p</italic>
< 0.001. At both incubation periods, there was a significant loss of mitochondrial membrane potential in PDT treated cells.</p>
</caption>
<graphic xlink:href="ijms-20-03254-g003"></graphic>
</fig>
<fig id="ijms-20-03254-f004" orientation="portrait" position="float">
<label>Figure 4</label>
<caption>
<p>Up- and down-regulated genes in DLD-1 cells summarizing the possible mode of cell death induced by ZnPcSmix-PDT. Red arrows show either up- or down-regulated genes. Up-regulated death receptor 6 (
<italic>DR6</italic>
) may signal mitochondrial-induced cell death or induction of inflammation. Rupturing of lysosomes releases acidic lysosomal contents such as cathepsins, consequently followed by activation of NAIP. NAIP and PYCARD play a role in preceding inflammatory actions via NFkB-1 activation. However, since
<italic>NFkB1</italic>
was up-regulated, and
<italic>MCL1</italic>
,
<italic>BCL2L2</italic>
and
<italic>BCL2L10</italic>
were down-regulated, evasion of apoptosis was unsuccessful thus leading to DNA damage and apoptosis.</p>
</caption>
<graphic xlink:href="ijms-20-03254-g004"></graphic>
</fig>
<fig id="ijms-20-03254-f005" orientation="portrait" position="float">
<label>Figure 5</label>
<caption>
<p>Possible mode of cell death pathway in Caco-2 cells. Red arrows show either up- or down-regulated genes. Tumor necrosis factor receptor (
<italic>TNFR</italic>
) was up-regulated, signaling its proactive role in the receptor induced pathway and involvement of Caspases that precede apoptotic nuclear damage.
<italic>TP53</italic>
(p53) activates pro-apoptotic genes (
<italic>BAK</italic>
and
<italic>BIK</italic>
), resulting in decreased mitochondrial membrane potential (MMP) and subsequent release of mitochondrial apoptotic contents such as cytochrome C (Cyto C) and direct IAP binding protein with low pI (
<italic>DIABLO</italic>
). DIABLO deactivates inhibitors of apoptosis proteins (IAPs) in order to potentiate apoptosis. Up-regulated
<italic>CD27</italic>
and
<italic>PYCARD</italic>
are suggestive of an inflammatory response; however,
<italic>NF
<sub>K</sub>
β1</italic>
was neither up- nor down-regulated in Caco-2 cells, hence the uncertainty (?) regarding the involvement of inflammasomes.</p>
</caption>
<graphic xlink:href="ijms-20-03254-g005"></graphic>
</fig>
<table-wrap id="ijms-20-03254-t001" orientation="portrait" position="float">
<object-id pub-id-type="pii">ijms-20-03254-t001_Table 1</object-id>
<label>Table 1</label>
<caption>
<p>Gene expression in DLD-1 cells. Up-regulated genes had a fold change (2
<sup>(−∆∆Ct)</sup>
) above 1, while down-regulated genes had a 2
<sup>(−∆∆Ct)</sup>
below 1. Only statistically significant genes are shown.</p>
</caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Gene Symbol</th>
<th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Gene Name</th>
<th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">
<italic>p</italic>
Value</th>
<th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Fold-Change 2
<sup>(−∆∆Ct)</sup>
</th>
<th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Up (↑)/Down (↓) Regulation</th>
<th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Function</th>
</tr>
</thead>
<tbody>
<tr>
<td align="center" valign="middle" rowspan="1" colspan="1">
<italic>ABL1</italic>
</td>
<td align="center" valign="middle" rowspan="1" colspan="1">ABL proto-oncogene 1, non-receptor tyrosine kinase</td>
<td align="center" valign="middle" rowspan="1" colspan="1"><0.05</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.29</td>
<td align="center" valign="middle" rowspan="1" colspan="1"></td>
<td align="center" valign="middle" rowspan="1" colspan="1">Positive Regulation of Apoptosis</td>
</tr>
<tr>
<td align="center" valign="middle" rowspan="1" colspan="1">
<italic>BAK1</italic>
</td>
<td align="center" valign="middle" rowspan="1" colspan="1">BCL2 antagonist/killer 1</td>
<td align="center" valign="middle" rowspan="1" colspan="1"><0.05</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.11</td>
<td align="center" valign="middle" rowspan="1" colspan="1"></td>
<td align="center" valign="middle" rowspan="1" colspan="1">Pro-Apoptotic/Positive Regulation of Apoptosis</td>
</tr>
<tr>
<td align="center" valign="middle" rowspan="1" colspan="1">
<italic>BCL2L10</italic>
</td>
<td align="center" valign="middle" rowspan="1" colspan="1">BCL2 like 10</td>
<td align="center" valign="middle" rowspan="1" colspan="1"><0.001</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.19</td>
<td align="center" valign="middle" rowspan="1" colspan="1"></td>
<td align="center" valign="middle" rowspan="1" colspan="1">Anti-Apoptotic</td>
</tr>
<tr>
<td align="center" valign="middle" rowspan="1" colspan="1">
<italic>BCL2L2</italic>
</td>
<td align="center" valign="middle" rowspan="1" colspan="1">BCL2 like 2</td>
<td align="center" valign="middle" rowspan="1" colspan="1"><0.05</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.07</td>
<td align="center" valign="middle" rowspan="1" colspan="1"></td>
<td align="center" valign="middle" rowspan="1" colspan="1">Anti-Apoptotic</td>
</tr>
<tr>
<td align="center" valign="middle" rowspan="1" colspan="1">
<italic>BID</italic>
</td>
<td align="center" valign="middle" rowspan="1" colspan="1">BH3 interacting domain death agonist</td>
<td align="center" valign="middle" rowspan="1" colspan="1"><0.05</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.29</td>
<td align="center" valign="middle" rowspan="1" colspan="1"></td>
<td align="center" valign="middle" rowspan="1" colspan="1">Pro-Apoptotic/Positive Regulation of Apoptosis</td>
</tr>
<tr>
<td align="center" valign="middle" rowspan="1" colspan="1">
<italic>CASP14</italic>
</td>
<td align="center" valign="middle" rowspan="1" colspan="1">Caspase 14</td>
<td align="center" valign="middle" rowspan="1" colspan="1"><0.001</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.19</td>
<td align="center" valign="middle" rowspan="1" colspan="1"></td>
<td align="center" valign="middle" rowspan="1" colspan="1">Pro-Apoptotic/Positive Regulation of Apoptosis/Caspase</td>
</tr>
<tr>
<td align="center" valign="middle" rowspan="1" colspan="1">
<italic>CD27</italic>
</td>
<td align="center" valign="middle" rowspan="1" colspan="1">CD27 molecule</td>
<td align="center" valign="middle" rowspan="1" colspan="1"><0.001</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.22</td>
<td align="center" valign="middle" rowspan="1" colspan="1"></td>
<td align="center" valign="middle" rowspan="1" colspan="1">Pro-Apoptotic/Anti-Apoptotic/Negative Regulation of Apoptosis/Caspase inhibitor</td>
</tr>
<tr>
<td align="center" valign="middle" rowspan="1" colspan="1">
<italic>CD40</italic>
</td>
<td align="center" valign="middle" rowspan="1" colspan="1">CD40 molecule</td>
<td align="center" valign="middle" rowspan="1" colspan="1"><0.001</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.22</td>
<td align="center" valign="middle" rowspan="1" colspan="1"></td>
<td align="center" valign="middle" rowspan="1" colspan="1">Positive Regulation of Apoptosis</td>
</tr>
<tr>
<td align="center" valign="middle" rowspan="1" colspan="1">
<italic>CD40LG</italic>
</td>
<td align="center" valign="middle" rowspan="1" colspan="1">CD40 ligand</td>
<td align="center" valign="middle" rowspan="1" colspan="1"><0.05</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.25</td>
<td align="center" valign="middle" rowspan="1" colspan="1"></td>
<td align="center" valign="middle" rowspan="1" colspan="1">Anti-Apoptotic</td>
</tr>
<tr>
<td align="center" valign="middle" rowspan="1" colspan="1">
<italic>CD70</italic>
</td>
<td align="center" valign="middle" rowspan="1" colspan="1">CD70 molecule</td>
<td align="center" valign="middle" rowspan="1" colspan="1"><0.01</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.28</td>
<td align="center" valign="middle" rowspan="1" colspan="1"></td>
<td align="center" valign="middle" rowspan="1" colspan="1">Pro-Apoptotic/Positive Regulation of Apoptosis</td>
</tr>
<tr>
<td align="center" valign="middle" rowspan="1" colspan="1">
<italic>CIDEA</italic>
</td>
<td align="center" valign="middle" rowspan="1" colspan="1">Cell death inducing DFFA like effector a</td>
<td align="center" valign="middle" rowspan="1" colspan="1"><0.01</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.17</td>
<td align="center" valign="middle" rowspan="1" colspan="1"></td>
<td align="center" valign="middle" rowspan="1" colspan="1">Negative Regulation of Apoptosis/DNA Damage & Repair</td>
</tr>
<tr>
<td align="center" valign="middle" rowspan="1" colspan="1">
<italic>IL10</italic>
</td>
<td align="center" valign="middle" rowspan="1" colspan="1">Interleukin 10</td>
<td align="center" valign="middle" rowspan="1" colspan="1"><0.05</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.24</td>
<td align="center" valign="middle" rowspan="1" colspan="1"></td>
<td align="center" valign="middle" rowspan="1" colspan="1">Anti-Apoptotic</td>
</tr>
<tr>
<td align="center" valign="middle" rowspan="1" colspan="1">
<italic>LTBR</italic>
</td>
<td align="center" valign="middle" rowspan="1" colspan="1">Lymphotoxin beta receptor</td>
<td align="center" valign="middle" rowspan="1" colspan="1"><0.001</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.10</td>
<td align="center" valign="middle" rowspan="1" colspan="1"></td>
<td align="center" valign="middle" rowspan="1" colspan="1">Positive Regulation of Apoptosis</td>
</tr>
<tr>
<td align="center" valign="middle" rowspan="1" colspan="1">
<italic>MCL1</italic>
</td>
<td align="center" valign="middle" rowspan="1" colspan="1">MCL1 apoptosis regulator, BCL2 family member</td>
<td align="center" valign="middle" rowspan="1" colspan="1"><0.01</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.10</td>
<td align="center" valign="middle" rowspan="1" colspan="1"></td>
<td align="center" valign="middle" rowspan="1" colspan="1">Negative Regulation of Apoptosis</td>
</tr>
<tr>
<td align="center" valign="middle" rowspan="1" colspan="1">
<italic>NAIP</italic>
</td>
<td align="center" valign="middle" rowspan="1" colspan="1">NLR family apoptosis inhibitory protein</td>
<td align="center" valign="middle" rowspan="1" colspan="1"><0.001</td>
<td align="center" valign="middle" rowspan="1" colspan="1">5.69</td>
<td align="center" valign="middle" rowspan="1" colspan="1"></td>
<td align="center" valign="middle" rowspan="1" colspan="1">Anti-Apoptotic/Negative Regulation of Apoptosis</td>
</tr>
<tr>
<td align="center" valign="middle" rowspan="1" colspan="1">
<italic>NFkB1</italic>
</td>
<td align="center" valign="middle" rowspan="1" colspan="1">Nuclear factor kappa B subunit 1</td>
<td align="center" valign="middle" rowspan="1" colspan="1"><0.01</td>
<td align="center" valign="middle" rowspan="1" colspan="1">3.09</td>
<td align="center" valign="middle" rowspan="1" colspan="1"></td>
<td align="center" valign="middle" rowspan="1" colspan="1">Anti-Apoptotic</td>
</tr>
<tr>
<td align="center" valign="middle" rowspan="1" colspan="1">
<italic>PYCARD</italic>
</td>
<td align="center" valign="middle" rowspan="1" colspan="1">PYD and CARD domain containing</td>
<td align="center" valign="middle" rowspan="1" colspan="1"><0.01</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.28</td>
<td align="center" valign="middle" rowspan="1" colspan="1"></td>
<td align="center" valign="middle" rowspan="1" colspan="1">Pro-Apoptotic/Positive Regulation of Apoptosis/Caspase Regulator</td>
</tr>
<tr>
<td align="center" valign="middle" rowspan="1" colspan="1">
<italic>RIPK2</italic>
</td>
<td align="center" valign="middle" rowspan="1" colspan="1">Receptor interacting serine/threonine kinase 2</td>
<td align="center" valign="middle" rowspan="1" colspan="1"><0.05</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.23</td>
<td align="center" valign="middle" rowspan="1" colspan="1"></td>
<td align="center" valign="middle" rowspan="1" colspan="1">Anti-Apoptotic/Positive Regulation of Apoptosis</td>
</tr>
<tr>
<td align="center" valign="middle" rowspan="1" colspan="1">
<italic>TNF</italic>
</td>
<td align="center" valign="middle" rowspan="1" colspan="1">Tumor necrosis factor</td>
<td align="center" valign="middle" rowspan="1" colspan="1"><0.05</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.70</td>
<td align="center" valign="middle" rowspan="1" colspan="1"></td>
<td align="center" valign="middle" rowspan="1" colspan="1">Death Domain Receptor/Anti-Apoptotic/Positive Regulation of Apoptosis</td>
</tr>
<tr>
<td align="center" valign="middle" rowspan="1" colspan="1">
<italic>TNFRSF21</italic>
</td>
<td align="center" valign="middle" rowspan="1" colspan="1">TNF receptor superfamily member 21</td>
<td align="center" valign="middle" rowspan="1" colspan="1"><0.01</td>
<td align="center" valign="middle" rowspan="1" colspan="1">284.18</td>
<td align="center" valign="middle" rowspan="1" colspan="1"></td>
<td align="center" valign="middle" rowspan="1" colspan="1">Death Domain Receptor</td>
</tr>
<tr>
<td align="center" valign="middle" rowspan="1" colspan="1">
<italic>TNFSF8</italic>
</td>
<td align="center" valign="middle" rowspan="1" colspan="1">TNF superfamily member 8</td>
<td align="center" valign="middle" rowspan="1" colspan="1"><0.001</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.18</td>
<td align="center" valign="middle" rowspan="1" colspan="1"></td>
<td align="center" valign="middle" rowspan="1" colspan="1">Pro-Apoptotic/Positive Regulation of Apoptosis</td>
</tr>
<tr>
<td align="center" valign="middle" rowspan="1" colspan="1">
<italic>TP73</italic>
</td>
<td align="center" valign="middle" rowspan="1" colspan="1">Tumor protein p73</td>
<td align="center" valign="middle" rowspan="1" colspan="1"><0.01</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.20</td>
<td align="center" valign="middle" rowspan="1" colspan="1"></td>
<td align="center" valign="middle" rowspan="1" colspan="1">DNA Damage & Repair/Negative Regulation of Apoptosis</td>
</tr>
<tr>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">
<italic>TRADD</italic>
</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">TNFRSF1A associated via death domain</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"><0.05</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">0.09</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Pro-Apoptotic/Positive Regulation of Apoptosis/Death Domain Receptor</td>
</tr>
</tbody>
</table>
</table-wrap>
<table-wrap id="ijms-20-03254-t002" orientation="portrait" position="float">
<object-id pub-id-type="pii">ijms-20-03254-t002_Table 2</object-id>
<label>Table 2</label>
<caption>
<p>Gene expression in Caco-2 cells 24 h post-PDT. Up-regulated genes had a fold change (2
<sup>(−∆∆Ct)</sup>
) above 1, while down-regulated genes had a 2
<sup>(−∆∆Ct)</sup>
below 1. Only statistically significant genes are shown.</p>
</caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Gene Symbol</th>
<th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Gene Name</th>
<th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">
<italic>p</italic>
Value</th>
<th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Fold-Change 2
<sup>(−∆∆Ct)</sup>
</th>
<th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Up (↑)/Down (↓) Regulation</th>
<th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Function</th>
</tr>
</thead>
<tbody>
<tr>
<td align="center" valign="middle" rowspan="1" colspan="1">
<italic>AKT1</italic>
</td>
<td align="center" valign="middle" rowspan="1" colspan="1">AKT serine/threonine kinase 1</td>
<td align="center" valign="middle" rowspan="1" colspan="1"><0.001</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.11</td>
<td align="center" valign="middle" rowspan="1" colspan="1"></td>
<td align="center" valign="middle" rowspan="1" colspan="1">Anti-Apoptotic/Positive Regulation of Apoptosis</td>
</tr>
<tr>
<td align="center" valign="middle" rowspan="1" colspan="1">
<italic>APAF1</italic>
</td>
<td align="center" valign="middle" rowspan="1" colspan="1">Apoptotic peptidase activating factor 1</td>
<td align="center" valign="middle" rowspan="1" colspan="1"><0.01</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.21</td>
<td align="center" valign="middle" rowspan="1" colspan="1"></td>
<td align="center" valign="middle" rowspan="1" colspan="1">Caspase Activator</td>
</tr>
<tr>
<td align="center" valign="middle" rowspan="1" colspan="1">
<italic>BAD</italic>
</td>
<td align="center" valign="middle" rowspan="1" colspan="1">BCL2 associated agonist of cell death</td>
<td align="center" valign="middle" rowspan="1" colspan="1"><0.01</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.29</td>
<td align="center" valign="middle" rowspan="1" colspan="1"></td>
<td align="center" valign="middle" rowspan="1" colspan="1">Pro-Apoptotic/Positive Regulation of Apoptosis</td>
</tr>
<tr>
<td align="center" valign="middle" rowspan="1" colspan="1">
<italic>BAK1</italic>
</td>
<td align="center" valign="middle" rowspan="1" colspan="1">BCL2 antagonist/killer 1</td>
<td align="center" valign="middle" rowspan="1" colspan="1"><0.05</td>
<td align="center" valign="middle" rowspan="1" colspan="1">3.07</td>
<td align="center" valign="middle" rowspan="1" colspan="1"></td>
<td align="center" valign="middle" rowspan="1" colspan="1">Pro-Apoptotic/Positive Regulation of Apoptosis</td>
</tr>
<tr>
<td align="center" valign="middle" rowspan="1" colspan="1">
<italic>BAX</italic>
</td>
<td align="center" valign="middle" rowspan="1" colspan="1">BCL2 associated X, apoptosis regulator</td>
<td align="center" valign="middle" rowspan="1" colspan="1"><0.001</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.24</td>
<td align="center" valign="middle" rowspan="1" colspan="1"></td>
<td align="center" valign="middle" rowspan="1" colspan="1">Pro-Apoptotic/Anti-Apoptotic/Positive Regulation of Apoptosis/Caspase Activator</td>
</tr>
<tr>
<td align="center" valign="middle" rowspan="1" colspan="1">
<italic>BCL2</italic>
</td>
<td align="center" valign="middle" rowspan="1" colspan="1">BCL2 apoptosis regulator</td>
<td align="center" valign="middle" rowspan="1" colspan="1"><0.001</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.22</td>
<td align="center" valign="middle" rowspan="1" colspan="1"></td>
<td align="center" valign="middle" rowspan="1" colspan="1">Anti-Apoptotic/Negative Regulation of Apoptosis</td>
</tr>
<tr>
<td align="center" valign="middle" rowspan="1" colspan="1">
<italic>BCL2L1</italic>
</td>
<td align="center" valign="middle" rowspan="1" colspan="1">BCL2 like 1</td>
<td align="center" valign="middle" rowspan="1" colspan="1"><0.01</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.19</td>
<td align="center" valign="middle" rowspan="1" colspan="1"></td>
<td align="center" valign="middle" rowspan="1" colspan="1">Anti-Apoptotic</td>
</tr>
<tr>
<td align="center" valign="middle" rowspan="1" colspan="1">
<italic>BCL2L10</italic>
</td>
<td align="center" valign="middle" rowspan="1" colspan="1">BCL2 like 10</td>
<td align="center" valign="middle" rowspan="1" colspan="1"><0.05</td>
<td align="center" valign="middle" rowspan="1" colspan="1">2.27</td>
<td align="center" valign="middle" rowspan="1" colspan="1"></td>
<td align="center" valign="middle" rowspan="1" colspan="1">Anti-Apoptotic/Negative Regulation of Apoptosis</td>
</tr>
<tr>
<td align="center" valign="middle" rowspan="1" colspan="1">
<italic>BCL2L11</italic>
</td>
<td align="center" valign="middle" rowspan="1" colspan="1">BCL2 like 11</td>
<td align="center" valign="middle" rowspan="1" colspan="1"><0.05</td>
<td align="center" valign="middle" rowspan="1" colspan="1">2.27</td>
<td align="center" valign="middle" rowspan="1" colspan="1"></td>
<td align="center" valign="middle" rowspan="1" colspan="1">Pro-Apoptotic</td>
</tr>
<tr>
<td align="center" valign="middle" rowspan="1" colspan="1">
<italic>BIK</italic>
</td>
<td align="center" valign="middle" rowspan="1" colspan="1">BCL2 interacting killer</td>
<td align="center" valign="middle" rowspan="1" colspan="1"><0.05</td>
<td align="center" valign="middle" rowspan="1" colspan="1">2.27</td>
<td align="center" valign="middle" rowspan="1" colspan="1"></td>
<td align="center" valign="middle" rowspan="1" colspan="1">Pro-Apoptotic/Positive Regulation of Apoptosis</td>
</tr>
<tr>
<td align="center" valign="middle" rowspan="1" colspan="1">
<italic>BIRC5</italic>
</td>
<td align="center" valign="middle" rowspan="1" colspan="1">Baculoviral IAP repeat containing 5</td>
<td align="center" valign="middle" rowspan="1" colspan="1"><0.01</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.23</td>
<td align="center" valign="middle" rowspan="1" colspan="1"></td>
<td align="center" valign="middle" rowspan="1" colspan="1">Anti-Apoptotic</td>
</tr>
<tr>
<td align="center" valign="middle" rowspan="1" colspan="1">
<italic>BNIP2</italic>
</td>
<td align="center" valign="middle" rowspan="1" colspan="1">BCL2 interacting protein 2</td>
<td align="center" valign="middle" rowspan="1" colspan="1"><0.05</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.38</td>
<td align="center" valign="middle" rowspan="1" colspan="1"></td>
<td align="center" valign="middle" rowspan="1" colspan="1">Anti-Apoptotic/Negative Regulation of Apoptosis</td>
</tr>
<tr>
<td align="center" valign="middle" rowspan="1" colspan="1">
<italic>CASP10</italic>
</td>
<td align="center" valign="middle" rowspan="1" colspan="1">Caspase 10</td>
<td align="center" valign="middle" rowspan="1" colspan="1"><0.05</td>
<td align="center" valign="middle" rowspan="1" colspan="1">2.27</td>
<td align="center" valign="middle" rowspan="1" colspan="1"></td>
<td align="center" valign="middle" rowspan="1" colspan="1">Positive Regulation of Apoptosis/Caspase</td>
</tr>
<tr>
<td align="center" valign="middle" rowspan="1" colspan="1">
<italic>CASP14</italic>
</td>
<td align="center" valign="middle" rowspan="1" colspan="1">Caspase 14</td>
<td align="center" valign="middle" rowspan="1" colspan="1"><0.05</td>
<td align="center" valign="middle" rowspan="1" colspan="1">2.27</td>
<td align="center" valign="middle" rowspan="1" colspan="1"></td>
<td align="center" valign="middle" rowspan="1" colspan="1">Pro-Apoptotic/Positive Regulation of Apoptosis/Caspase</td>
</tr>
<tr>
<td align="center" valign="middle" rowspan="1" colspan="1">
<italic>CASP2</italic>
</td>
<td align="center" valign="middle" rowspan="1" colspan="1">Caspase 2</td>
<td align="center" valign="middle" rowspan="1" colspan="1"><0.001</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.19</td>
<td align="center" valign="middle" rowspan="1" colspan="1"></td>
<td align="center" valign="middle" rowspan="1" colspan="1">Pro-Apoptotic/Positive Regulation of Apoptosis/Caspase</td>
</tr>
<tr>
<td align="center" valign="middle" rowspan="1" colspan="1">
<italic>CASP6</italic>
</td>
<td align="center" valign="middle" rowspan="1" colspan="1">Caspase 6</td>
<td align="center" valign="middle" rowspan="1" colspan="1"><0.001</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.53</td>
<td align="center" valign="middle" rowspan="1" colspan="1"></td>
<td align="center" valign="middle" rowspan="1" colspan="1">Pro-Apoptotic/Positive Regulation of Apoptosis/Caspase</td>
</tr>
<tr>
<td align="center" valign="middle" rowspan="1" colspan="1">
<italic>CASP8</italic>
</td>
<td align="center" valign="middle" rowspan="1" colspan="1">Caspase 8</td>
<td align="center" valign="middle" rowspan="1" colspan="1"><0.01</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.34</td>
<td align="center" valign="middle" rowspan="1" colspan="1"></td>
<td align="center" valign="middle" rowspan="1" colspan="1">Pro-Apoptotic/Positive Regulation of Apoptosis/Caspase</td>
</tr>
<tr>
<td align="center" valign="middle" rowspan="1" colspan="1">
<italic>CD27</italic>
</td>
<td align="center" valign="middle" rowspan="1" colspan="1">CD27 molecule</td>
<td align="center" valign="middle" rowspan="1" colspan="1"><0.05</td>
<td align="center" valign="middle" rowspan="1" colspan="1">1.99</td>
<td align="center" valign="middle" rowspan="1" colspan="1"></td>
<td align="center" valign="middle" rowspan="1" colspan="1">Pro-Apoptotic/Anti-Apoptotic/Negative Regulation of Apoptosis/Caspase inhibitor</td>
</tr>
<tr>
<td align="center" valign="middle" rowspan="1" colspan="1">
<italic>CD40LG</italic>
</td>
<td align="center" valign="middle" rowspan="1" colspan="1">CD40 ligand</td>
<td align="center" valign="middle" rowspan="1" colspan="1"><0.01</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.40</td>
<td align="center" valign="middle" rowspan="1" colspan="1"></td>
<td align="center" valign="middle" rowspan="1" colspan="1">Anti-Apoptotic</td>
</tr>
<tr>
<td align="center" valign="middle" rowspan="1" colspan="1">
<italic>CIDEA</italic>
</td>
<td align="center" valign="middle" rowspan="1" colspan="1">Cell death inducing DFFA like effector a</td>
<td align="center" valign="middle" rowspan="1" colspan="1"><0.05</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.20</td>
<td align="center" valign="middle" rowspan="1" colspan="1"></td>
<td align="center" valign="middle" rowspan="1" colspan="1">Negative Regulation of Apoptosis/DNA Damage & Repair</td>
</tr>
<tr>
<td align="center" valign="middle" rowspan="1" colspan="1">
<italic>CYCS</italic>
</td>
<td align="center" valign="middle" rowspan="1" colspan="1">Cytochrome c, somatic</td>
<td align="center" valign="middle" rowspan="1" colspan="1"><0.01</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.34</td>
<td align="center" valign="middle" rowspan="1" colspan="1"></td>
<td align="center" valign="middle" rowspan="1" colspan="1">Pro-Apoptotic</td>
</tr>
<tr>
<td align="center" valign="middle" rowspan="1" colspan="1">
<italic>DIABLO</italic>
</td>
<td align="center" valign="middle" rowspan="1" colspan="1">Diablo IAP-binding mitochondrial protein</td>
<td align="center" valign="middle" rowspan="1" colspan="1"><0.001</td>
<td align="center" valign="middle" rowspan="1" colspan="1">7.82</td>
<td align="center" valign="middle" rowspan="1" colspan="1"></td>
<td align="center" valign="middle" rowspan="1" colspan="1">Pro-Apoptotic</td>
</tr>
<tr>
<td align="center" valign="middle" rowspan="1" colspan="1">
<italic>FADD</italic>
</td>
<td align="center" valign="middle" rowspan="1" colspan="1">Fas associated via death domain</td>
<td align="center" valign="middle" rowspan="1" colspan="1"><0.05</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.18</td>
<td align="center" valign="middle" rowspan="1" colspan="1"></td>
<td align="center" valign="middle" rowspan="1" colspan="1">Positive Regulation of Apoptosis/Death Domain</td>
</tr>
<tr>
<td align="center" valign="middle" rowspan="1" colspan="1">
<italic>FASLG</italic>
</td>
<td align="center" valign="middle" rowspan="1" colspan="1">Fas ligand</td>
<td align="center" valign="middle" rowspan="1" colspan="1"><0.01</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.23</td>
<td align="center" valign="middle" rowspan="1" colspan="1"></td>
<td align="center" valign="middle" rowspan="1" colspan="1">Pro-Apoptotic/Positive Regulation of Apoptosis</td>
</tr>
<tr>
<td align="center" valign="middle" rowspan="1" colspan="1">
<italic>GADD45A</italic>
</td>
<td align="center" valign="middle" rowspan="1" colspan="1">Growth arrest and DNA damage inducible alpha</td>
<td align="center" valign="middle" rowspan="1" colspan="1"><0.03</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.58</td>
<td align="center" valign="middle" rowspan="1" colspan="1"></td>
<td align="center" valign="middle" rowspan="1" colspan="1">Pro-Apoptotic</td>
</tr>
<tr>
<td align="center" valign="middle" rowspan="1" colspan="1">
<italic>IGF1R</italic>
</td>
<td align="center" valign="middle" rowspan="1" colspan="1">Insulin like growth factor 1 receptor</td>
<td align="center" valign="middle" rowspan="1" colspan="1"><0.001</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.13</td>
<td align="center" valign="middle" rowspan="1" colspan="1"></td>
<td align="center" valign="middle" rowspan="1" colspan="1">Anti-Apoptotic/Negative Regulation of Apoptosis</td>
</tr>
<tr>
<td align="center" valign="middle" rowspan="1" colspan="1">
<italic>LTBR</italic>
</td>
<td align="center" valign="middle" rowspan="1" colspan="1">Lymphotoxin beta receptor</td>
<td align="center" valign="middle" rowspan="1" colspan="1"><0.01</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.42</td>
<td align="center" valign="middle" rowspan="1" colspan="1"></td>
<td align="center" valign="middle" rowspan="1" colspan="1">Positive Regulation of Apoptosis</td>
</tr>
<tr>
<td align="center" valign="middle" rowspan="1" colspan="1">
<italic>MCL1</italic>
</td>
<td align="center" valign="middle" rowspan="1" colspan="1">MCL1 apoptosis regulator, BCL2 family member</td>
<td align="center" valign="middle" rowspan="1" colspan="1"><0.01</td>
<td align="center" valign="middle" rowspan="1" colspan="1">2.27</td>
<td align="center" valign="middle" rowspan="1" colspan="1"></td>
<td align="center" valign="middle" rowspan="1" colspan="1">Negative Regulation of Apoptosis</td>
</tr>
<tr>
<td align="center" valign="middle" rowspan="1" colspan="1">
<italic>NAIP</italic>
</td>
<td align="center" valign="middle" rowspan="1" colspan="1">NLR family apoptosis inhibitory protein</td>
<td align="center" valign="middle" rowspan="1" colspan="1"><0.05</td>
<td align="center" valign="middle" rowspan="1" colspan="1">2.27</td>
<td align="center" valign="middle" rowspan="1" colspan="1"></td>
<td align="center" valign="middle" rowspan="1" colspan="1">Anti-Apoptotic/Negative Regulation of Apoptosis</td>
</tr>
<tr>
<td align="center" valign="middle" rowspan="1" colspan="1">
<italic>PYCARD</italic>
</td>
<td align="center" valign="middle" rowspan="1" colspan="1">PYD and CARD domain containing</td>
<td align="center" valign="middle" rowspan="1" colspan="1"><0.05</td>
<td align="center" valign="middle" rowspan="1" colspan="1">2.73</td>
<td align="center" valign="middle" rowspan="1" colspan="1"></td>
<td align="center" valign="middle" rowspan="1" colspan="1">Pro-Apoptotic/Positive Regulation of Apoptosis/Caspase Regulator</td>
</tr>
<tr>
<td align="center" valign="middle" rowspan="1" colspan="1">
<italic>RIPK2</italic>
</td>
<td align="center" valign="middle" rowspan="1" colspan="1">Receptor interacting serine/threonine kinase 2</td>
<td align="center" valign="middle" rowspan="1" colspan="1"><0.01</td>
<td align="center" valign="middle" rowspan="1" colspan="1">2.28</td>
<td align="center" valign="middle" rowspan="1" colspan="1"></td>
<td align="center" valign="middle" rowspan="1" colspan="1">Anti-Apoptotic/Positive Regulation of Apoptosis</td>
</tr>
<tr>
<td align="center" valign="middle" rowspan="1" colspan="1">
<italic>TNF</italic>
</td>
<td align="center" valign="middle" rowspan="1" colspan="1">Tumor necrosis factor</td>
<td align="center" valign="middle" rowspan="1" colspan="1"><0.05</td>
<td align="center" valign="middle" rowspan="1" colspan="1">2.27</td>
<td align="center" valign="middle" rowspan="1" colspan="1"></td>
<td align="center" valign="middle" rowspan="1" colspan="1">Death Domain Receptor/Anti-Apoptotic/Positive Regulation of Apoptosis</td>
</tr>
<tr>
<td align="center" valign="middle" rowspan="1" colspan="1">
<italic>TNFRSF10A</italic>
</td>
<td align="center" valign="middle" rowspan="1" colspan="1">TNF receptor superfamily member 10a</td>
<td align="center" valign="middle" rowspan="1" colspan="1"><0.05</td>
<td align="center" valign="middle" rowspan="1" colspan="1">2.06</td>
<td align="center" valign="middle" rowspan="1" colspan="1"></td>
<td align="center" valign="middle" rowspan="1" colspan="1">Pro-Apoptotic/Positive Regulation of Apoptosis/Death Domain Receptor</td>
</tr>
<tr>
<td align="center" valign="middle" rowspan="1" colspan="1">
<italic>TNFRSF9</italic>
</td>
<td align="center" valign="middle" rowspan="1" colspan="1">TNF receptor superfamily member 9</td>
<td align="center" valign="middle" rowspan="1" colspan="1"><0.05</td>
<td align="center" valign="middle" rowspan="1" colspan="1">2.27</td>
<td align="center" valign="middle" rowspan="1" colspan="1"></td>
<td align="center" valign="middle" rowspan="1" colspan="1">Pro-Apoptotic/Positive Regulation of Apoptosis</td>
</tr>
<tr>
<td align="center" valign="middle" rowspan="1" colspan="1">
<italic>TNFSF8</italic>
</td>
<td align="center" valign="middle" rowspan="1" colspan="1">TNF superfamily member 8</td>
<td align="center" valign="middle" rowspan="1" colspan="1"><0.05</td>
<td align="center" valign="middle" rowspan="1" colspan="1">2.27</td>
<td align="center" valign="middle" rowspan="1" colspan="1"></td>
<td align="center" valign="middle" rowspan="1" colspan="1">Pro-Apoptotic/Positive Regulation of Apoptosis</td>
</tr>
<tr>
<td align="center" valign="middle" rowspan="1" colspan="1">
<italic>TP53</italic>
</td>
<td align="center" valign="middle" rowspan="1" colspan="1">Tumor protein p53</td>
<td align="center" valign="middle" rowspan="1" colspan="1"><0.01</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.38</td>
<td align="center" valign="middle" rowspan="1" colspan="1"></td>
<td align="center" valign="middle" rowspan="1" colspan="1">DNA Damage & Repair/Positive Regulation of Apoptosis/Caspase Activator</td>
</tr>
<tr>
<td align="center" valign="middle" rowspan="1" colspan="1">
<italic>TP73</italic>
</td>
<td align="center" valign="middle" rowspan="1" colspan="1">Tumor protein p73</td>
<td align="center" valign="middle" rowspan="1" colspan="1"><0.05</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.22</td>
<td align="center" valign="middle" rowspan="1" colspan="1"></td>
<td align="center" valign="middle" rowspan="1" colspan="1">DNA Damage & Repair/Negative Regulation of Apoptosis</td>
</tr>
<tr>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">
<italic>TRADD</italic>
</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">TNFRSF1A associated via death domain</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"><0.05</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">0.32</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Pro-Apoptotic/Positive Regulation of Apoptosis/Death Domain Receptor</td>
</tr>
</tbody>
</table>
</table-wrap>
<table-wrap id="ijms-20-03254-t003" orientation="portrait" position="float">
<object-id pub-id-type="pii">ijms-20-03254-t003_Table 3</object-id>
<label>Table 3</label>
<caption>
<p>Functional genes that were analyzed simultaneously on the human apoptosis RT
<sup>2</sup>
Profiler™ PCR array.</p>
</caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Functional Gene Grouping</th>
<th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Genes</th>
</tr>
</thead>
<tbody>
<tr>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Death Domain Receptors</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">
<italic>CRADD</italic>
,
<italic>FADD</italic>
,
<italic>TNF</italic>
,
<italic>TNFRSF10B</italic>
(
<italic>DR5</italic>
).</td>
</tr>
<tr>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">DNA Damage & Repair</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">
<italic>ANL1</italic>
,
<italic>CIDEA</italic>
,
<italic>CIDEB</italic>
,
<italic>TP53</italic>
,
<italic>TP73</italic>
.</td>
</tr>
<tr>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Extracellular Apoptotic Signals</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">
<italic>CFLAR</italic>
(
<italic>CASPER</italic>
),
<italic>DAPK1</italic>
,
<italic>TNFRSF25</italic>
(
<italic>DR3</italic>
).</td>
</tr>
<tr>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Other Pro-Apoptotic Genes</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">
<italic>BAD</italic>
,
<italic>BAK1</italic>
,
<italic>BAX</italic>
,
<italic>BCL10</italic>
,
<italic>BCL2L11</italic>
,
<italic>BID</italic>
,
<italic>BIK</italic>
,
<italic>BNIP3</italic>
,
<italic>BNIP3L</italic>
,
<italic>CASP1</italic>
(
<italic>ICE</italic>
),
<italic>CSP10</italic>
(
<italic>MCH4</italic>
),
<italic>CASP14</italic>
,
<italic>CASP2</italic>
,
<italic>CASP3</italic>
,
<italic>CASP4</italic>
,
<italic>CASP6</italic>
,
<italic>CASP8</italic>
,
<italic>CD27</italic>
(
<italic>TNFRSF7</italic>
),
<italic>CD70</italic>
(
<italic>TNFSF7</italic>
),
<italic>CYCS</italic>
,
<italic>DFFA</italic>
,
<italic>DIABLO</italic>
(
<italic>SMAC</italic>
),
<italic>FAS</italic>
(
<italic>TNFRSF6</italic>
),
<italic>FASLG</italic>
(
<italic>TNFSF6</italic>
),
<italic>GADD45A</italic>
,
<italic>HRK</italic>
,
<italic>LTA</italic>
(
<italic>TNFB</italic>
),
<italic>NOD1</italic>
(
<italic>CARD4</italic>
),
<italic>PYCARD</italic>
(
<italic>TMS1/ASC</italic>
),
<italic>TNFRSF10A</italic>
,
<italic>TNFRSF9</italic>
,
<italic>TNFSF10</italic>
(
<italic>TRAIL</italic>
),
<italic>TNFSF8. TP53BP2</italic>
,
<italic>TRADD</italic>
,
<italic>TRAF3</italic>
.</td>
</tr>
<tr>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Anti-Apoptotic</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">
<italic>AKT1</italic>
,
<italic>BAG1</italic>
,
<italic>BAG3</italic>
,
<italic>BAX</italic>
,
<italic>BCL2</italic>
,
<italic>BCL2A1</italic>
(
<italic>Bfl-1/A1</italic>
),
<italic>BCL2L1</italic>
(
<italic>BCL-X</italic>
),
<italic>BCL2L10</italic>
,
<italic>BCL2L2</italic>
,
<italic>BFAR</italic>
,
<italic>BIRC3</italic>
(
<italic>cIAP1</italic>
),
<italic>BIRC5</italic>
,
<italic>BIRC6</italic>
,
<italic>BNIP2</italic>
,
<italic>BNIP3</italic>
,
<italic>BNIP3L</italic>
,
<italic>BRAF</italic>
,
<italic>CD27</italic>
(
<italic>TNFRSF7</italic>
),
<italic>CD40LG</italic>
(
<italic>TNFSF5</italic>
),
<italic>CFLAR</italic>
(
<italic>CASPER</italic>
,
<italic>DAPK1</italic>
,
<italic>FAS</italic>
(
<italic>TNFRSF6</italic>
,
<italic>HRK</italic>
,
<italic>IGF1R</italic>
,
<italic>IL10</italic>
,
<italic>MCK1</italic>
,
<italic>NAIP</italic>
(
<italic>BIRC1</italic>
),
<italic>NFKB1</italic>
,
<italic>NOL3</italic>
,
<italic>RIPK2</italic>
,
<italic>TNF</italic>
,
<italic>XIAP</italic>
(
<italic>BIRC4</italic>
).</td>
</tr>
<tr>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Regulation of Apoptosis</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">
<bold>Negative regulation:</bold>
<italic>BAG1</italic>
,
<italic>BAG3</italic>
,
<italic>BCL10</italic>
,
<italic>BCL2</italic>
,
<italic>BCL2A1</italic>
(
<italic>Bfl-1/A1</italic>
),
<italic>BCL2L1</italic>
(
<italic>BCL-X</italic>
),
<italic>BCL2L10</italic>
,
<italic>BCL2L2</italic>
,
<italic>BFAR</italic>
,
<italic>BIRC2</italic>
(
<italic>c-IAP2</italic>
),
<italic>BIRC3</italic>
(
<italic>c-IAP1</italic>
),
<italic>BIRC6</italic>
,
<italic>BNIP2</italic>
,
<italic>BNIP3</italic>
,
<italic>BNIP3L</italic>
,
<italic>BRAF</italic>
,
<italic>CASP3</italic>
,
<italic>CD27</italic>
(
<italic>TNFRSF7</italic>
),
<italic>CD40LG</italic>
(
<italic>TNFSF5</italic>
),
<italic>CFLAR</italic>
(
<italic>CASPER</italic>
),
<italic>CIDEA</italic>
,
<italic>DAPK1</italic>
,
<italic>DFFA</italic>
,
<italic>FAS</italic>
(
<italic>TNFRSF6</italic>
),
<italic>IGF1R</italic>
,
<italic>MCL1</italic>
,
<italic>NAIP</italic>
(
<italic>BIRC1</italic>
),
<italic>NOL3</italic>
,
<italic>TP53</italic>
,
<italic>TP73</italic>
,
<italic>XIAP</italic>
(
<italic>BIRC4</italic>
).
<break></break>
<bold>Positive regulation:</bold>
<italic>ABL1</italic>
,
<italic>AKT1</italic>
,
<italic>BAD</italic>
,
<italic>BAK1</italic>
,
<italic>BAX</italic>
,
<italic>BCL2L11</italic>
,
<italic>BID</italic>
,
<italic>BIK</italic>
,
<italic>BNIP3</italic>
,
<italic>BNIP3L</italic>
,
<italic>CASP1</italic>
(
<italic>ICE</italic>
),
<italic>CASP10</italic>
(
<italic>MCH4</italic>
),
<italic>CASP14</italic>
,
<italic>CASP2</italic>
,
<italic>CASP4</italic>
,
<italic>CASP6</italic>
,
<italic>CASP8</italic>
,
<italic>CD40</italic>
(
<italic>TNFRSF5</italic>
),
<italic>CD70</italic>
(
<italic>TNFSF7</italic>
),
<italic>CIDEB</italic>
,
<italic>CRADD</italic>
,
<italic>FADD</italic>
,
<italic>FASLG</italic>
(
<italic>TNFSF6</italic>
),
<italic>HRK</italic>
,
<italic>LTA</italic>
(
<italic>TNFB</italic>
),
<italic>LTBR</italic>
,
<italic>NOD1</italic>
(
<italic>CARD4</italic>
),
<italic>PYCARD</italic>
(
<italic>TMSS1/ASC</italic>
),
<italic>RIPK2</italic>
,
<italic>TNF</italic>
,
<italic>TNFRSF10A</italic>
,
<italic>TNFRSF10B</italic>
(
<italic>DR5</italic>
),
<italic>TNFRSF25</italic>
(
<italic>DR3</italic>
),
<italic>TNFRSF9</italic>
,
<italic>TNFSF10</italic>
(
<italic>TRAIL</italic>
),
<italic>TNFSF8</italic>
,
<italic>TP53</italic>
,
<italic>TP53BP2</italic>
,
<italic>TRADD</italic>
,
<italic>TRAF2</italic>
,
<italic>TRAF3</italic>
.</td>
</tr>
<tr>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Death Domain Receptors</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">
<italic>CRADD</italic>
,
<italic>DAPK1</italic>
,
<italic>FADD</italic>
,
<italic>TNFRSF10A</italic>
,
<italic>TNFRSF10B</italic>
(
<italic>DR5</italic>
),
<italic>TNFRSF11B</italic>
,
<italic>TNFRSF1A</italic>
,
<italic>TNFRSF1B</italic>
,
<italic>TNFRSF21</italic>
,
<italic>TNFRSF25</italic>
(
<italic>DR3</italic>
),
<italic>TRADD</italic>
. </td>
</tr>
<tr>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Caspases and Regulators </td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">
<bold>Caspases:</bold>
<italic>CASP1</italic>
(
<italic>ICE</italic>
),
<italic>CASP10</italic>
(
<italic>MCH4</italic>
),
<italic>CASP14</italic>
,
<italic>CASP2</italic>
,
<italic>CASP3</italic>
,
<italic>CASP4</italic>
,
<italic>CASP5</italic>
,
<italic>CASP6</italic>
,
<italic>CASP7</italic>
,
<italic>CASP8</italic>
,
<italic>CASP9</italic>
,
<italic>CFLAR</italic>
(
<italic>CASPER</italic>
),
<italic>CRADD</italic>
,
<italic>PYCARD</italic>
(
<italic>TMS1/ASC</italic>
).
<break></break>
<bold>Caspase activators:</bold>
<italic>AIFM1</italic>
(
<italic>PDCD8</italic>
),
<italic>APAF1</italic>
,
<italic>BAX</italic>
,
<italic>BCL2L10</italic>
,
<italic>CASP1</italic>
(
<italic>ICE</italic>
),
<italic>CASP9</italic>
,
<italic>NOD</italic>
(
<italic>CARD4</italic>
),
<italic>PYCARD</italic>
(
<italic>TMS1/ASC</italic>
),
<italic>TNFRSF10A</italic>
,
<italic>TNFRSF10B</italic>
(
<italic>DR5</italic>
),
<italic>TP53</italic>
.
<break></break>
<bold>Caspase inhibitors:</bold>
<italic>CD27</italic>
(
<italic>TNFRSF7</italic>
),
<italic>XIAP</italic>
(
<italic>BIRC4</italic>
).</td>
</tr>
</tbody>
</table>
</table-wrap>
</floats-group>
</pmc>
<affiliations>
<list></list>
<tree>
<noCountry>
<name sortKey="Abrahamse, Heidi" sort="Abrahamse, Heidi" uniqKey="Abrahamse H" first="Heidi" last="Abrahamse">Heidi Abrahamse</name>
<name sortKey="Houreld, Nicolette Nadene" sort="Houreld, Nicolette Nadene" uniqKey="Houreld N" first="Nicolette Nadene" last="Houreld">Nicolette Nadene Houreld</name>
</noCountry>
</tree>
</affiliations>
</record>

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