Thymoquinone Enhances Paclitaxel Anti-Breast Cancer Activity via Inhibiting Tumor-Associated Stem Cells Despite Apparent Mathematical Antagonism
Identifieur interne : 000725 ( Pmc/Curation ); précédent : 000724; suivant : 000726Thymoquinone Enhances Paclitaxel Anti-Breast Cancer Activity via Inhibiting Tumor-Associated Stem Cells Despite Apparent Mathematical Antagonism
Auteurs : Hanan A. Bashmail ; Aliaa A. Alamoudi ; Abdulwahab Noorwali ; Gehan A. Hegazy [Égypte] ; Ghada M. Ajabnoor ; Ahmed M. Al-Abd [Égypte]Source :
- Molecules [ 1420-3049 ] ; 2020.
Abstract
Thymoquinone (TQ) has shown substantial evidence for its anticancer effects. Using human breast cancer cells, we evaluated the chemomodulatory effect of TQ on paclitaxel (PTX). TQ showed weak cytotoxic properties against MCF-7 and T47D breast cancer cells with IC50 values of 64.93 ± 14 µM and 165 ± 2 µM, respectively. Combining TQ with PTX showed apparent antagonism, increasing the IC50 values of PTX from 0.2 ± 0.07 µM to 0.7 ± 0.01 µM and from 0.1 ± 0.01 µM to 0.15 ± 0.02 µM in MCF-7 and T47D cells, respectively. Combination index analysis showed antagonism in both cell lines with CI values of 4.6 and 1.6, respectively. However, resistance fractions to PTX within MCF-7 and T47D cells (42.3 ± 1.4% and 41.9 ± 1.1%, respectively) were completely depleted by combination with TQ. TQ minimally affected the cell cycle, with moderate accumulation of cells in the S-phase. However, a significant increase in Pre-G phase cells was observed due to PTX alone and PTX combination with TQ. To dissect this increase in the Pre-G phase, apoptosis, necrosis, and autophagy were assessed by flowcytometry. TQ significantly increased the percent of apoptotic/necrotic cell death in T47D cells after combination with paclitaxel. On the other hand, TQ significantly induced autophagy in MCF-7 cells. Furthermore, TQ was found to significantly decrease breast cancer-associated stem cell clone (CD44+/CD24-cell) in both MCF-7 and T47D cells. This was mirrored by the downregulation of TWIST-1 gene and overexpression of SNAIL-1 and SNAIL-2 genes. TQ therefore possesses potential chemomodulatory effects to PTX when studied in breast cancer cells via enhancing PTX induced cell death including autophagy. In addition, TQ depletes breast cancer-associated stem cells and sensitizes breast cancer cells to PTX killing effects.
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DOI: 10.3390/molecules25020426
PubMed: 31968657
PubMed Central: 7024316
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Ahmed M. Al-Abd<affiliation><nlm:aff id="af3-molecules-25-00426">Department of Pharmaceutical Sciences, College of Pharmacy, Gulf Medical University, Ajman 4184, UAE</nlm:aff><wicri:noCountry code="subfield">UAE</wicri:noCountry></affiliation><affiliation wicri:level="1"><nlm:aff id="af4-molecules-25-00426">Department of Pharmacology, Medical Division, National Research Centre, Giza 12622, Egypt</nlm:aff><country xml:lang="fr">Égypte</country><wicri:regionArea>Department of Pharmacology, Medical Division, National Research Centre, Giza 12622</wicri:regionArea></affiliation>Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Thymoquinone Enhances Paclitaxel Anti-Breast Cancer Activity via Inhibiting Tumor-Associated Stem Cells Despite Apparent Mathematical Antagonism</title><author><name sortKey="Bashmail, Hanan A" sort="Bashmail, Hanan A" uniqKey="Bashmail H" first="Hanan A." last="Bashmail">Hanan A. Bashmail</name><affiliation><nlm:aff id="af1-molecules-25-00426">Department of Clinical Biochemistry, Faculty of Medicine, King Abdulaziz University, Jeddah 21589, Saudi Arabia;<email>hanan.a.bashmail@gmail.com</email> (H.A.B.);<email>aliaa.alamo@gmail.com</email> (A.A.A.);<email>wal5566@gmail.com</email> (A.N.);<email>gehanhegazy@hotmail.com</email> (G.A.H.);<email>ga_clinbio@yahoo.com</email> (G.M.A.)</nlm:aff></affiliation></author><author><name sortKey="Alamoudi, Aliaa A" sort="Alamoudi, Aliaa A" uniqKey="Alamoudi A" first="Aliaa A." last="Alamoudi">Aliaa A. Alamoudi</name><affiliation><nlm:aff id="af1-molecules-25-00426">Department of Clinical Biochemistry, Faculty of Medicine, King Abdulaziz University, Jeddah 21589, Saudi Arabia;<email>hanan.a.bashmail@gmail.com</email> (H.A.B.);<email>aliaa.alamo@gmail.com</email> (A.A.A.);<email>wal5566@gmail.com</email> (A.N.);<email>gehanhegazy@hotmail.com</email> (G.A.H.);<email>ga_clinbio@yahoo.com</email> (G.M.A.)</nlm:aff></affiliation></author><author><name sortKey="Noorwali, Abdulwahab" sort="Noorwali, Abdulwahab" uniqKey="Noorwali A" first="Abdulwahab" last="Noorwali">Abdulwahab Noorwali</name><affiliation><nlm:aff id="af1-molecules-25-00426">Department of Clinical Biochemistry, Faculty of Medicine, King Abdulaziz University, Jeddah 21589, Saudi Arabia;<email>hanan.a.bashmail@gmail.com</email> (H.A.B.);<email>aliaa.alamo@gmail.com</email> (A.A.A.);<email>wal5566@gmail.com</email> (A.N.);<email>gehanhegazy@hotmail.com</email> (G.A.H.);<email>ga_clinbio@yahoo.com</email> (G.M.A.)</nlm:aff></affiliation></author><author><name sortKey="Hegazy, Gehan A" sort="Hegazy, Gehan A" uniqKey="Hegazy G" first="Gehan A." last="Hegazy">Gehan A. Hegazy</name><affiliation><nlm:aff id="af1-molecules-25-00426">Department of Clinical Biochemistry, Faculty of Medicine, King Abdulaziz University, Jeddah 21589, Saudi Arabia;<email>hanan.a.bashmail@gmail.com</email> (H.A.B.);<email>aliaa.alamo@gmail.com</email> (A.A.A.);<email>wal5566@gmail.com</email> (A.N.);<email>gehanhegazy@hotmail.com</email> (G.A.H.);<email>ga_clinbio@yahoo.com</email> (G.M.A.)</nlm:aff></affiliation><affiliation wicri:level="1"><nlm:aff id="af2-molecules-25-00426">Department of Medical Biochemistry, Medical Division, National Research Centre, Giza 12622, Egypt</nlm:aff><country xml:lang="fr">Égypte</country><wicri:regionArea>Department of Medical Biochemistry, Medical Division, National Research Centre, Giza 12622</wicri:regionArea></affiliation></author><author><name sortKey="Ajabnoor, Ghada M" sort="Ajabnoor, Ghada M" uniqKey="Ajabnoor G" first="Ghada M." last="Ajabnoor">Ghada M. Ajabnoor</name><affiliation><nlm:aff id="af1-molecules-25-00426">Department of Clinical Biochemistry, Faculty of Medicine, King Abdulaziz University, Jeddah 21589, Saudi Arabia;<email>hanan.a.bashmail@gmail.com</email> (H.A.B.);<email>aliaa.alamo@gmail.com</email> (A.A.A.);<email>wal5566@gmail.com</email> (A.N.);<email>gehanhegazy@hotmail.com</email> (G.A.H.);<email>ga_clinbio@yahoo.com</email> (G.M.A.)</nlm:aff></affiliation></author><author><name sortKey="Al Abd, Ahmed M" sort="Al Abd, Ahmed M" uniqKey="Al Abd A" first="Ahmed M." last="Al-Abd">Ahmed M. Al-Abd</name><affiliation><nlm:aff id="af3-molecules-25-00426">Department of Pharmaceutical Sciences, College of Pharmacy, Gulf Medical University, Ajman 4184, UAE</nlm:aff><wicri:noCountry code="subfield">UAE</wicri:noCountry></affiliation><affiliation wicri:level="1"><nlm:aff id="af4-molecules-25-00426">Department of Pharmacology, Medical Division, National Research Centre, Giza 12622, Egypt</nlm:aff><country xml:lang="fr">Égypte</country><wicri:regionArea>Department of Pharmacology, Medical Division, National Research Centre, Giza 12622</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">31968657</idno><idno type="pmc">7024316</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7024316</idno><idno type="RBID">PMC:7024316</idno><idno type="doi">10.3390/molecules25020426</idno><date when="2020">2020</date><idno type="wicri:Area/Pmc/Corpus">000725</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000725</idno><idno type="wicri:Area/Pmc/Curation">000725</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000725</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Thymoquinone Enhances Paclitaxel Anti-Breast Cancer Activity via Inhibiting Tumor-Associated Stem Cells Despite Apparent Mathematical Antagonism</title><author><name sortKey="Bashmail, Hanan A" sort="Bashmail, Hanan A" uniqKey="Bashmail H" first="Hanan A." last="Bashmail">Hanan A. Bashmail</name><affiliation><nlm:aff id="af1-molecules-25-00426">Department of Clinical Biochemistry, Faculty of Medicine, King Abdulaziz University, Jeddah 21589, Saudi Arabia;<email>hanan.a.bashmail@gmail.com</email> (H.A.B.);<email>aliaa.alamo@gmail.com</email> (A.A.A.);<email>wal5566@gmail.com</email> (A.N.);<email>gehanhegazy@hotmail.com</email> (G.A.H.);<email>ga_clinbio@yahoo.com</email> (G.M.A.)</nlm:aff></affiliation></author><author><name sortKey="Alamoudi, Aliaa A" sort="Alamoudi, Aliaa A" uniqKey="Alamoudi A" first="Aliaa A." last="Alamoudi">Aliaa A. Alamoudi</name><affiliation><nlm:aff id="af1-molecules-25-00426">Department of Clinical Biochemistry, Faculty of Medicine, King Abdulaziz University, Jeddah 21589, Saudi Arabia;<email>hanan.a.bashmail@gmail.com</email> (H.A.B.);<email>aliaa.alamo@gmail.com</email> (A.A.A.);<email>wal5566@gmail.com</email> (A.N.);<email>gehanhegazy@hotmail.com</email> (G.A.H.);<email>ga_clinbio@yahoo.com</email> (G.M.A.)</nlm:aff></affiliation></author><author><name sortKey="Noorwali, Abdulwahab" sort="Noorwali, Abdulwahab" uniqKey="Noorwali A" first="Abdulwahab" last="Noorwali">Abdulwahab Noorwali</name><affiliation><nlm:aff id="af1-molecules-25-00426">Department of Clinical Biochemistry, Faculty of Medicine, King Abdulaziz University, Jeddah 21589, Saudi Arabia;<email>hanan.a.bashmail@gmail.com</email> (H.A.B.);<email>aliaa.alamo@gmail.com</email> (A.A.A.);<email>wal5566@gmail.com</email> (A.N.);<email>gehanhegazy@hotmail.com</email> (G.A.H.);<email>ga_clinbio@yahoo.com</email> (G.M.A.)</nlm:aff></affiliation></author><author><name sortKey="Hegazy, Gehan A" sort="Hegazy, Gehan A" uniqKey="Hegazy G" first="Gehan A." last="Hegazy">Gehan A. Hegazy</name><affiliation><nlm:aff id="af1-molecules-25-00426">Department of Clinical Biochemistry, Faculty of Medicine, King Abdulaziz University, Jeddah 21589, Saudi Arabia;<email>hanan.a.bashmail@gmail.com</email> (H.A.B.);<email>aliaa.alamo@gmail.com</email> (A.A.A.);<email>wal5566@gmail.com</email> (A.N.);<email>gehanhegazy@hotmail.com</email> (G.A.H.);<email>ga_clinbio@yahoo.com</email> (G.M.A.)</nlm:aff></affiliation><affiliation wicri:level="1"><nlm:aff id="af2-molecules-25-00426">Department of Medical Biochemistry, Medical Division, National Research Centre, Giza 12622, Egypt</nlm:aff><country xml:lang="fr">Égypte</country><wicri:regionArea>Department of Medical Biochemistry, Medical Division, National Research Centre, Giza 12622</wicri:regionArea></affiliation></author><author><name sortKey="Ajabnoor, Ghada M" sort="Ajabnoor, Ghada M" uniqKey="Ajabnoor G" first="Ghada M." last="Ajabnoor">Ghada M. Ajabnoor</name><affiliation><nlm:aff id="af1-molecules-25-00426">Department of Clinical Biochemistry, Faculty of Medicine, King Abdulaziz University, Jeddah 21589, Saudi Arabia;<email>hanan.a.bashmail@gmail.com</email> (H.A.B.);<email>aliaa.alamo@gmail.com</email> (A.A.A.);<email>wal5566@gmail.com</email> (A.N.);<email>gehanhegazy@hotmail.com</email> (G.A.H.);<email>ga_clinbio@yahoo.com</email> (G.M.A.)</nlm:aff></affiliation></author><author><name sortKey="Al Abd, Ahmed M" sort="Al Abd, Ahmed M" uniqKey="Al Abd A" first="Ahmed M." last="Al-Abd">Ahmed M. Al-Abd</name><affiliation><nlm:aff id="af3-molecules-25-00426">Department of Pharmaceutical Sciences, College of Pharmacy, Gulf Medical University, Ajman 4184, UAE</nlm:aff><wicri:noCountry code="subfield">UAE</wicri:noCountry></affiliation><affiliation wicri:level="1"><nlm:aff id="af4-molecules-25-00426">Department of Pharmacology, Medical Division, National Research Centre, Giza 12622, Egypt</nlm:aff><country xml:lang="fr">Égypte</country><wicri:regionArea>Department of Pharmacology, Medical Division, National Research Centre, Giza 12622</wicri:regionArea></affiliation></author></analytic><series><title level="j">Molecules</title><idno type="eISSN">1420-3049</idno><imprint><date when="2020">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Thymoquinone (TQ) has shown substantial evidence for its anticancer effects. Using human breast cancer cells, we evaluated the chemomodulatory effect of TQ on paclitaxel (PTX). TQ showed weak cytotoxic properties against MCF-7 and T47D breast cancer cells with IC<sub>50</sub> values of 64.93 ± 14 µM and 165 ± 2 µM, respectively. Combining TQ with PTX showed apparent antagonism, increasing the IC<sub>50</sub> values of PTX from 0.2 ± 0.07 µM to 0.7 ± 0.01 µM and from 0.1 ± 0.01 µM to 0.15 ± 0.02 µM in MCF-7 and T47D cells, respectively. Combination index analysis showed antagonism in both cell lines with CI values of 4.6 and 1.6, respectively. However, resistance fractions to PTX within MCF-7 and T47D cells (42.3 ± 1.4% and 41.9 ± 1.1%, respectively) were completely depleted by combination with TQ. TQ minimally affected the cell cycle, with moderate accumulation of cells in the S-phase. However, a significant increase in Pre-G phase cells was observed due to PTX alone and PTX combination with TQ. To dissect this increase in the Pre-G phase, apoptosis, necrosis, and autophagy were assessed by flowcytometry. TQ significantly increased the percent of apoptotic/necrotic cell death in T47D cells after combination with paclitaxel. On the other hand, TQ significantly induced autophagy in MCF-7 cells. Furthermore, TQ was found to significantly decrease breast cancer-associated stem cell clone (CD44+/CD24-cell) in both MCF-7 and T47D cells. This was mirrored by the downregulation of TWIST-1 gene and overexpression of SNAIL-1 and SNAIL-2 genes. TQ therefore possesses potential chemomodulatory effects to PTX when studied in breast cancer cells via enhancing PTX induced cell death including autophagy. In addition, TQ depletes breast cancer-associated stem cells and sensitizes breast cancer cells to PTX killing effects.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Clardy, J" uniqKey="Clardy J">J. 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<front><journal-meta><journal-id journal-id-type="nlm-ta">Molecules</journal-id><journal-id journal-id-type="iso-abbrev">Molecules</journal-id><journal-id journal-id-type="publisher-id">molecules</journal-id><journal-title-group><journal-title>Molecules</journal-title></journal-title-group><issn pub-type="epub">1420-3049</issn><publisher><publisher-name>MDPI</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">31968657</article-id><article-id pub-id-type="pmc">7024316</article-id><article-id pub-id-type="doi">10.3390/molecules25020426</article-id><article-id pub-id-type="publisher-id">molecules-25-00426</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Thymoquinone Enhances Paclitaxel Anti-Breast Cancer Activity via Inhibiting Tumor-Associated Stem Cells Despite Apparent Mathematical Antagonism</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Bashmail</surname><given-names>Hanan A.</given-names></name><xref ref-type="aff" rid="af1-molecules-25-00426">1</xref></contrib><contrib contrib-type="author"><name><surname>Alamoudi</surname><given-names>Aliaa A.</given-names></name><xref ref-type="aff" rid="af1-molecules-25-00426">1</xref></contrib><contrib contrib-type="author"><name><surname>Noorwali</surname><given-names>Abdulwahab</given-names></name><xref ref-type="aff" rid="af1-molecules-25-00426">1</xref></contrib><contrib contrib-type="author"><name><surname>Hegazy</surname><given-names>Gehan A.</given-names></name><xref ref-type="aff" rid="af1-molecules-25-00426">1</xref><xref ref-type="aff" rid="af2-molecules-25-00426">2</xref></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid" authenticated="true">https://orcid.org/0000-0001-9096-1531</contrib-id><name><surname>Ajabnoor</surname><given-names>Ghada M.</given-names></name><xref ref-type="aff" rid="af1-molecules-25-00426">1</xref></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid" authenticated="true">https://orcid.org/0000-0001-7872-4867</contrib-id><name><surname>Al-Abd</surname><given-names>Ahmed M.</given-names></name><xref ref-type="aff" rid="af3-molecules-25-00426">3</xref><xref ref-type="aff" rid="af4-molecules-25-00426">4</xref><xref rid="c1-molecules-25-00426" ref-type="corresp">*</xref></contrib></contrib-group><contrib-group><contrib contrib-type="editor"><name><surname>Brestic</surname><given-names>Marian</given-names></name><role>Academic Editor</role></contrib></contrib-group><aff id="af1-molecules-25-00426"><label>1</label>Department of Clinical Biochemistry, Faculty of Medicine, King Abdulaziz University, Jeddah 21589, Saudi Arabia;<email>hanan.a.bashmail@gmail.com</email> (H.A.B.);<email>aliaa.alamo@gmail.com</email> (A.A.A.);<email>wal5566@gmail.com</email> (A.N.);<email>gehanhegazy@hotmail.com</email> (G.A.H.);<email>ga_clinbio@yahoo.com</email> (G.M.A.)</aff><aff id="af2-molecules-25-00426"><label>2</label>Department of Medical Biochemistry, Medical Division, National Research Centre, Giza 12622, Egypt</aff><aff id="af3-molecules-25-00426"><label>3</label>Department of Pharmaceutical Sciences, College of Pharmacy, Gulf Medical University, Ajman 4184, UAE</aff><aff id="af4-molecules-25-00426"><label>4</label>Department of Pharmacology, Medical Division, National Research Centre, Giza 12622, Egypt</aff><author-notes><corresp id="c1-molecules-25-00426"><label>*</label>Correspondence: <email>ahmedmalabd@pharma.asu.edu.eg</email>; Tel.: +971-(0)56-464-2929</corresp></author-notes><pub-date pub-type="epub"><day>20</day><month>1</month><year>2020</year></pub-date><pub-date pub-type="collection"><month>1</month><year>2020</year></pub-date><volume>25</volume><issue>2</issue><elocation-id>426</elocation-id><history><date date-type="received"><day>04</day><month>12</month><year>2019</year></date><date date-type="accepted"><day>17</day><month>1</month><year>2020</year></date></history><permissions><copyright-statement>© 2020 by the authors.</copyright-statement><copyright-year>2020</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>Thymoquinone (TQ) has shown substantial evidence for its anticancer effects. Using human breast cancer cells, we evaluated the chemomodulatory effect of TQ on paclitaxel (PTX). TQ showed weak cytotoxic properties against MCF-7 and T47D breast cancer cells with IC<sub>50</sub> values of 64.93 ± 14 µM and 165 ± 2 µM, respectively. Combining TQ with PTX showed apparent antagonism, increasing the IC<sub>50</sub> values of PTX from 0.2 ± 0.07 µM to 0.7 ± 0.01 µM and from 0.1 ± 0.01 µM to 0.15 ± 0.02 µM in MCF-7 and T47D cells, respectively. Combination index analysis showed antagonism in both cell lines with CI values of 4.6 and 1.6, respectively. However, resistance fractions to PTX within MCF-7 and T47D cells (42.3 ± 1.4% and 41.9 ± 1.1%, respectively) were completely depleted by combination with TQ. TQ minimally affected the cell cycle, with moderate accumulation of cells in the S-phase. However, a significant increase in Pre-G phase cells was observed due to PTX alone and PTX combination with TQ. To dissect this increase in the Pre-G phase, apoptosis, necrosis, and autophagy were assessed by flowcytometry. TQ significantly increased the percent of apoptotic/necrotic cell death in T47D cells after combination with paclitaxel. On the other hand, TQ significantly induced autophagy in MCF-7 cells. Furthermore, TQ was found to significantly decrease breast cancer-associated stem cell clone (CD44+/CD24-cell) in both MCF-7 and T47D cells. This was mirrored by the downregulation of TWIST-1 gene and overexpression of SNAIL-1 and SNAIL-2 genes. TQ therefore possesses potential chemomodulatory effects to PTX when studied in breast cancer cells via enhancing PTX induced cell death including autophagy. In addition, TQ depletes breast cancer-associated stem cells and sensitizes breast cancer cells to PTX killing effects.</p></abstract><kwd-group><kwd>paclitaxel</kwd><kwd>thymoquinone</kwd><kwd>apoptosis</kwd><kwd>autophagy</kwd><kwd>tumor-associated stem cells</kwd></kwd-group></article-meta></front><floats-group><fig id="molecules-25-00426-f001" orientation="portrait" position="float"><label>Figure 1</label><caption><p>The effect of thymoquinone (TQ) on the dose-response curve of paclitaxel (PTX) in MCF-7 (<bold>A</bold>) and T47D (<bold>B</bold>) breast cancer cell lines. Cells were exposed to the serial dilution of PTX, TQ, or their combination for 72 h. Cell viability was determined using a sulfarodamine-B (SRB) assay, and data are expressed as mean ± SD (<italic>n</italic> = 3).</p></caption><graphic xlink:href="molecules-25-00426-g001"></graphic></fig><fig id="molecules-25-00426-f002" orientation="portrait" position="float"><label>Figure 2</label><caption><p>Effect of PTX, TQ, and their combination on the cell cycle distribution of MCF-7 cells. Cells were exposed to PTX, TQ, or their combination for 24 h (<bold>A</bold>,<bold>C</bold>) or 48 h (<bold>B</bold>,<bold>D</bold>). Cell cycle distribution was determined using DNA content flowcytometry analysis and different cell phases were plotted as percentage of total events. Sub-G cell population was plotted as percent of total events (<bold>C</bold>,<bold>D</bold>). Data are presented as mean ± SD; <italic>n</italic> = 3. (*) significantly different from the control group.</p></caption><graphic xlink:href="molecules-25-00426-g002"></graphic></fig><fig id="molecules-25-00426-f003" orientation="portrait" position="float"><label>Figure 3</label><caption><p>Effect of PTX, TQ, and their combination on the cell cycle distribution of T47D cells. Cells were exposed to PTX, TQ, or their combination for 24 h (<bold>A</bold>,<bold>C</bold>) or 48 h (<bold>B</bold>,<bold>D</bold>). Cell cycle distribution was determined using DNA content flowcytometry analysis and different cell phases were plotted as percentage of total events. Sub-G cell population was plotted as percent of total events (<bold>C</bold>,<bold>D</bold>). Data are presented as mean ± SD; <italic>n</italic> = 3. (*) significantly different from the control group. (**) significantly different from PTX treatment.</p></caption><graphic xlink:href="molecules-25-00426-g003"></graphic></fig><fig id="molecules-25-00426-f004" orientation="portrait" position="float"><label>Figure 4</label><caption><p>Apoptosis/necrosis assessment in T47D cells after exposure to PTX, TQ, and their combination. Cells were exposed to PTX, TQ, or their combination for 24 h (<bold>A</bold>) and 48 h (<bold>B</bold>). Cells were stained with annexin V-FITC/PI and different cell populations are plotted as a percentage of total events. Western blot analysis for caspase-3 and PARP was assessed for MCF-7 (<bold>C</bold>) and T47D (<bold>D</bold>) cells. Data are presented as mean ± SD; <italic>n</italic> = 3. (*) significantly different from the control group. (**) significantly different from PTX treatment.</p></caption><graphic xlink:href="molecules-25-00426-g004"></graphic></fig><fig id="molecules-25-00426-f005" orientation="portrait" position="float"><label>Figure 5</label><caption><p>Autophagic cell death assessment in MCF-7 (<bold>A</bold>) and T47D (<bold>B</bold>) cells after exposure to PTX, TQ, and their combination. Cells were exposed to PTX, TQ, or their combination for 24 h, and were stained with a Cyto-ID autophagosome tracker. Net fluorescent intensity (NFI) was plotted and compared to the basal fluorescence of the control group. Gene expression fold changes for beclin-I and LC3-II were assessed for MCF-7 (C) and T47D cells (<bold>D</bold>). Data are presented as mean ± SD; <italic>n</italic> = 3. (*) significantly different from the control group.</p></caption><graphic xlink:href="molecules-25-00426-g005"></graphic></fig><fig id="molecules-25-00426-f006" orientation="portrait" position="float"><label>Figure 6</label><caption><p>Effect of PTX, TQ, and their combination on the expression of CD44 and CD24 stem cell markers. MCF-7 (<bold>A</bold>) and T47D (<bold>B</bold>) cells were exposed to PTX, TQ, or their combination for 24 h. Expression levels of CD44 and CD24 were assessed using flowcytometry and plotted as percentage of total events. Data are presented as mean ± SD; <italic>n</italic> = 3. (*) significantly different from the control group. (**) significantly different from PTX treatment.</p></caption><graphic xlink:href="molecules-25-00426-g006"></graphic></fig><fig id="molecules-25-00426-f007" orientation="portrait" position="float"><label>Figure 7</label><caption><p>Effect of PTX and TQ on the expression of EMT-related genes in MCF-7 cells. Cells were exposed PTX or TQ for 24 h. Total RNA was extracted and subjected to RT-qPCR to measure gene expression. Data were plotted using the 2-ΔΔCt method (expression normalized to the housekeeping gene GAPDH). Fold expression and significance was calculated relative to control untreated cells (dotted line). Data are presented as mean ± SD; <italic>n</italic> = 3. (*) significantly different from the control group.</p></caption><graphic xlink:href="molecules-25-00426-g007"></graphic></fig><table-wrap id="molecules-25-00426-t001" orientation="portrait" position="float"><object-id pub-id-type="pii">molecules-25-00426-t001_Table 1</object-id><label>Table 1</label><caption><p>Combination analysis of cell cytotoxicity for TQ, PTX, and their combination against MCF-7 and T47D breast cancer cell lines.</p></caption><table frame="hsides" rules="groups"><thead><tr><th align="left" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1"></th><th colspan="2" align="left" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1">MCF-7</th><th colspan="2" align="left" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1">T47D</th></tr><tr><th align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></th><th align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">IC50 (µM)</th><th align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">R-Value (%)</th><th align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">IC50 (µM)</th><th align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">R-Value (%)</th></tr></thead><tbody><tr><td align="left" valign="middle" rowspan="1" colspan="1">PTX</td><td align="left" valign="middle" rowspan="1" colspan="1">0.2 ± 0.07</td><td align="left" valign="middle" rowspan="1" colspan="1">42.3 ± 1.4</td><td align="left" valign="middle" rowspan="1" colspan="1">0.1 ± 0.01</td><td align="left" valign="middle" rowspan="1" colspan="1">41.9 ± 1.1</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">TQ</td><td align="left" valign="middle" rowspan="1" colspan="1">64.9 ± 14.5</td><td align="left" valign="middle" rowspan="1" colspan="1">1.6 ± 1.3</td><td align="left" valign="middle" rowspan="1" colspan="1">165.1 ± 2.8</td><td align="left" valign="middle" rowspan="1" colspan="1">0.1 ± 0.15</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">PTX+TQ</td><td align="left" valign="middle" rowspan="1" colspan="1">0.7 ± 0.01</td><td align="left" valign="middle" rowspan="1" colspan="1">0</td><td align="left" valign="middle" rowspan="1" colspan="1">0.15 ± 0.02</td><td align="left" valign="middle" rowspan="1" colspan="1">0</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">CI-value </td><td colspan="2" align="left" valign="middle" style="border-bottom:solid thin" rowspan="1">Antagonism/4.6</td><td colspan="2" align="left" valign="middle" style="border-bottom:solid thin" rowspan="1">Antagonism/1.6</td></tr></tbody></table></table-wrap></floats-group></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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