A Potent Autophagy Inhibitor (Lys05) Enhances the Impact of Ionizing Radiation on Human Lung Cancer Cells H1299
Identifieur interne : 000B42 ( Main/Exploration ); précédent : 000B41; suivant : 000B43A Potent Autophagy Inhibitor (Lys05) Enhances the Impact of Ionizing Radiation on Human Lung Cancer Cells H1299
Auteurs : Lucie Cechakova ; Martin Ondrej ; Vojtech Pavlik [République tchèque] ; Petr Jost ; Dana Cizkova ; Ales Bezrouk ; Jaroslav Pejchal ; Ravi K. Amaravadi ; Jeffrey D. Winkler ; Ales TichySource :
- International Journal of Molecular Sciences [ 1422-0067 ] ; 2019.
Abstract
Autophagy inhibition through small-molecule inhibitors is one of the approaches to increase the efficiency of radiotherapy in oncological patients. A new inhibitor—Lys05—with the potential to accumulate within lysosomes and to block autophagy was discovered a few years ago. Several studies have addressed its chemosensitizing effects but nothing is known about its impact in the context of ionizing radiation (IR). To describe its role in radiosensitization, we employed radioresistant human non-small cell lung carcinoma cells (H1299, p53-negative). Combined treatment of H1299 cells by Lys05 together with IR decreased cell survival in the clonogenic assay and real-time monitoring of cell growth more than either Lys05 or IR alone. Immunodetection of LC3 and p62/SQSTM1 indicated that autophagy was inhibited, which correlated with increased
Url:
DOI: 10.3390/ijms20235881
PubMed: 31771188
PubMed Central: 6928878
Affiliations:
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">A Potent Autophagy Inhibitor (Lys05) Enhances the Impact of Ionizing Radiation on Human Lung Cancer Cells H1299</title><author><name sortKey="Cechakova, Lucie" sort="Cechakova, Lucie" uniqKey="Cechakova L" first="Lucie" last="Cechakova">Lucie Cechakova</name><affiliation><nlm:aff id="af1-ijms-20-05881">Department of Radiobiology, Faculty of Military Health Sciences, University of Defense in Brno, 500 01 Hradec Kralove, Czech Republic;<email>lucie.cechakova@unob.cz</email> (L.C.);<email>martin.ondrej@unob.cz</email> (M.O.)</nlm:aff></affiliation></author><author><name sortKey="Ondrej, Martin" sort="Ondrej, Martin" uniqKey="Ondrej M" first="Martin" last="Ondrej">Martin Ondrej</name><affiliation><nlm:aff id="af1-ijms-20-05881">Department of Radiobiology, Faculty of Military Health Sciences, University of Defense in Brno, 500 01 Hradec Kralove, Czech Republic;<email>lucie.cechakova@unob.cz</email> (L.C.);<email>martin.ondrej@unob.cz</email> (M.O.)</nlm:aff></affiliation></author><author><name sortKey="Pavlik, Vojtech" sort="Pavlik, Vojtech" uniqKey="Pavlik V" first="Vojtech" last="Pavlik">Vojtech Pavlik</name><affiliation><nlm:aff id="af2-ijms-20-05881">Cell Physiology Research Group, Contipro, 561 02 Dolni Dobrouc, Czech Republic;<email>vojtech.pavlik@contipro.com</email></nlm:aff></affiliation><affiliation wicri:level="1"><nlm:aff id="af3-ijms-20-05881">Institute of Dermatology, Third Faculty of Medicine, Charles University in Prague, 100 00 Prague 10-Vinohrady, Czech Republic</nlm:aff><country xml:lang="fr">République tchèque</country><wicri:regionArea>Institute of Dermatology, Third Faculty of Medicine, Charles University in Prague, 100 00 Prague 10-Vinohrady</wicri:regionArea><wicri:noRegion>100 00 Prague 10-Vinohrady</wicri:noRegion></affiliation></author><author><name sortKey="Jost, Petr" sort="Jost, Petr" uniqKey="Jost P" first="Petr" last="Jost">Petr Jost</name><affiliation><nlm:aff id="af4-ijms-20-05881">Department of Toxicology and Military Pharmacy, Faculty of Military Health Sciences, University of Defense in Brno, 500 01 Hradec Kralove, Czech Republic;<email>petr.jost@unob.cz</email> (P.J.);<email>jaroslav.pejchal@unob.cz</email> (J.P.)</nlm:aff></affiliation></author><author><name sortKey="Cizkova, Dana" sort="Cizkova, Dana" uniqKey="Cizkova D" first="Dana" last="Cizkova">Dana Cizkova</name><affiliation><nlm:aff id="af5-ijms-20-05881">Department of Histology and Embryology, Faculty of Medicine in Hradec Kralove, Charles University in Prague, 500 01 Hradec Kralove, Czech Republic;<email>CizkovaD@lfhk.cuni.cz</email></nlm:aff></affiliation></author><author><name sortKey="Bezrouk, Ales" sort="Bezrouk, Ales" uniqKey="Bezrouk A" first="Ales" last="Bezrouk">Ales Bezrouk</name><affiliation><nlm:aff id="af6-ijms-20-05881">Department of Medical Biophysics, Faculty of Medicine in Hradec Kralove, Charles University in Prague, 500 01 Hradec Kralove, Czech Republic;<email>BezroukA@lfhk.cuni.cz</email></nlm:aff></affiliation></author><author><name sortKey="Pejchal, Jaroslav" sort="Pejchal, Jaroslav" uniqKey="Pejchal J" first="Jaroslav" last="Pejchal">Jaroslav Pejchal</name><affiliation><nlm:aff id="af4-ijms-20-05881">Department of Toxicology and Military Pharmacy, Faculty of Military Health Sciences, University of Defense in Brno, 500 01 Hradec Kralove, Czech Republic;<email>petr.jost@unob.cz</email> (P.J.);<email>jaroslav.pejchal@unob.cz</email> (J.P.)</nlm:aff></affiliation></author><author><name sortKey="Amaravadi, Ravi K" sort="Amaravadi, Ravi K" uniqKey="Amaravadi R" first="Ravi K." last="Amaravadi">Ravi K. Amaravadi</name><affiliation><nlm:aff id="af7-ijms-20-05881">Abramson Cancer Center and Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA;<email>Ravi.Amaravadi@uphs.upenn.edu</email> (R.K.A.);<email>winkler@sas.upenn.edu</email> (J.D.W.)</nlm:aff></affiliation></author><author><name sortKey="Winkler, Jeffrey D" sort="Winkler, Jeffrey D" uniqKey="Winkler J" first="Jeffrey D." last="Winkler">Jeffrey D. Winkler</name><affiliation><nlm:aff id="af7-ijms-20-05881">Abramson Cancer Center and Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA;<email>Ravi.Amaravadi@uphs.upenn.edu</email> (R.K.A.);<email>winkler@sas.upenn.edu</email> (J.D.W.)</nlm:aff></affiliation></author><author><name sortKey="Tichy, Ales" sort="Tichy, Ales" uniqKey="Tichy A" first="Ales" last="Tichy">Ales Tichy</name><affiliation><nlm:aff id="af1-ijms-20-05881">Department of Radiobiology, Faculty of Military Health Sciences, University of Defense in Brno, 500 01 Hradec Kralove, Czech Republic;<email>lucie.cechakova@unob.cz</email> (L.C.);<email>martin.ondrej@unob.cz</email> (M.O.)</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">31771188</idno><idno type="pmc">6928878</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6928878</idno><idno type="RBID">PMC:6928878</idno><idno type="doi">10.3390/ijms20235881</idno><date when="2019">2019</date><idno type="wicri:Area/Pmc/Corpus">000619</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000619</idno><idno type="wicri:Area/Pmc/Curation">000619</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000619</idno><idno type="wicri:Area/Pmc/Checkpoint">000A65</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000A65</idno><idno type="wicri:Area/Ncbi/Merge">000C48</idno><idno type="wicri:Area/Ncbi/Curation">000C48</idno><idno type="wicri:Area/Ncbi/Checkpoint">000C48</idno><idno type="wicri:Area/Main/Merge">000B42</idno><idno type="wicri:Area/Main/Curation">000B42</idno><idno type="wicri:Area/Main/Exploration">000B42</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">A Potent Autophagy Inhibitor (Lys05) Enhances the Impact of Ionizing Radiation on Human Lung Cancer Cells H1299</title><author><name sortKey="Cechakova, Lucie" sort="Cechakova, Lucie" uniqKey="Cechakova L" first="Lucie" last="Cechakova">Lucie Cechakova</name><affiliation><nlm:aff id="af1-ijms-20-05881">Department of Radiobiology, Faculty of Military Health Sciences, University of Defense in Brno, 500 01 Hradec Kralove, Czech Republic;<email>lucie.cechakova@unob.cz</email> (L.C.);<email>martin.ondrej@unob.cz</email> (M.O.)</nlm:aff></affiliation></author><author><name sortKey="Ondrej, Martin" sort="Ondrej, Martin" uniqKey="Ondrej M" first="Martin" last="Ondrej">Martin Ondrej</name><affiliation><nlm:aff id="af1-ijms-20-05881">Department of Radiobiology, Faculty of Military Health Sciences, University of Defense in Brno, 500 01 Hradec Kralove, Czech Republic;<email>lucie.cechakova@unob.cz</email> (L.C.);<email>martin.ondrej@unob.cz</email> (M.O.)</nlm:aff></affiliation></author><author><name sortKey="Pavlik, Vojtech" sort="Pavlik, Vojtech" uniqKey="Pavlik V" first="Vojtech" last="Pavlik">Vojtech Pavlik</name><affiliation><nlm:aff id="af2-ijms-20-05881">Cell Physiology Research Group, Contipro, 561 02 Dolni Dobrouc, Czech Republic;<email>vojtech.pavlik@contipro.com</email></nlm:aff></affiliation><affiliation wicri:level="1"><nlm:aff id="af3-ijms-20-05881">Institute of Dermatology, Third Faculty of Medicine, Charles University in Prague, 100 00 Prague 10-Vinohrady, Czech Republic</nlm:aff><country xml:lang="fr">République tchèque</country><wicri:regionArea>Institute of Dermatology, Third Faculty of Medicine, Charles University in Prague, 100 00 Prague 10-Vinohrady</wicri:regionArea><wicri:noRegion>100 00 Prague 10-Vinohrady</wicri:noRegion></affiliation></author><author><name sortKey="Jost, Petr" sort="Jost, Petr" uniqKey="Jost P" first="Petr" last="Jost">Petr Jost</name><affiliation><nlm:aff id="af4-ijms-20-05881">Department of Toxicology and Military Pharmacy, Faculty of Military Health Sciences, University of Defense in Brno, 500 01 Hradec Kralove, Czech Republic;<email>petr.jost@unob.cz</email> (P.J.);<email>jaroslav.pejchal@unob.cz</email> (J.P.)</nlm:aff></affiliation></author><author><name sortKey="Cizkova, Dana" sort="Cizkova, Dana" uniqKey="Cizkova D" first="Dana" last="Cizkova">Dana Cizkova</name><affiliation><nlm:aff id="af5-ijms-20-05881">Department of Histology and Embryology, Faculty of Medicine in Hradec Kralove, Charles University in Prague, 500 01 Hradec Kralove, Czech Republic;<email>CizkovaD@lfhk.cuni.cz</email></nlm:aff></affiliation></author><author><name sortKey="Bezrouk, Ales" sort="Bezrouk, Ales" uniqKey="Bezrouk A" first="Ales" last="Bezrouk">Ales Bezrouk</name><affiliation><nlm:aff id="af6-ijms-20-05881">Department of Medical Biophysics, Faculty of Medicine in Hradec Kralove, Charles University in Prague, 500 01 Hradec Kralove, Czech Republic;<email>BezroukA@lfhk.cuni.cz</email></nlm:aff></affiliation></author><author><name sortKey="Pejchal, Jaroslav" sort="Pejchal, Jaroslav" uniqKey="Pejchal J" first="Jaroslav" last="Pejchal">Jaroslav Pejchal</name><affiliation><nlm:aff id="af4-ijms-20-05881">Department of Toxicology and Military Pharmacy, Faculty of Military Health Sciences, University of Defense in Brno, 500 01 Hradec Kralove, Czech Republic;<email>petr.jost@unob.cz</email> (P.J.);<email>jaroslav.pejchal@unob.cz</email> (J.P.)</nlm:aff></affiliation></author><author><name sortKey="Amaravadi, Ravi K" sort="Amaravadi, Ravi K" uniqKey="Amaravadi R" first="Ravi K." last="Amaravadi">Ravi K. Amaravadi</name><affiliation><nlm:aff id="af7-ijms-20-05881">Abramson Cancer Center and Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA;<email>Ravi.Amaravadi@uphs.upenn.edu</email> (R.K.A.);<email>winkler@sas.upenn.edu</email> (J.D.W.)</nlm:aff></affiliation></author><author><name sortKey="Winkler, Jeffrey D" sort="Winkler, Jeffrey D" uniqKey="Winkler J" first="Jeffrey D." last="Winkler">Jeffrey D. Winkler</name><affiliation><nlm:aff id="af7-ijms-20-05881">Abramson Cancer Center and Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA;<email>Ravi.Amaravadi@uphs.upenn.edu</email> (R.K.A.);<email>winkler@sas.upenn.edu</email> (J.D.W.)</nlm:aff></affiliation></author><author><name sortKey="Tichy, Ales" sort="Tichy, Ales" uniqKey="Tichy A" first="Ales" last="Tichy">Ales Tichy</name><affiliation><nlm:aff id="af1-ijms-20-05881">Department of Radiobiology, Faculty of Military Health Sciences, University of Defense in Brno, 500 01 Hradec Kralove, Czech Republic;<email>lucie.cechakova@unob.cz</email> (L.C.);<email>martin.ondrej@unob.cz</email> (M.O.)</nlm:aff></affiliation></author></analytic><series><title level="j">International Journal of Molecular Sciences</title><idno type="eISSN">1422-0067</idno><imprint><date when="2019">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Autophagy inhibition through small-molecule inhibitors is one of the approaches to increase the efficiency of radiotherapy in oncological patients. A new inhibitor—Lys05—with the potential to accumulate within lysosomes and to block autophagy was discovered a few years ago. Several studies have addressed its chemosensitizing effects but nothing is known about its impact in the context of ionizing radiation (IR). To describe its role in radiosensitization, we employed radioresistant human non-small cell lung carcinoma cells (H1299, p53-negative). Combined treatment of H1299 cells by Lys05 together with IR decreased cell survival in the clonogenic assay and real-time monitoring of cell growth more than either Lys05 or IR alone. Immunodetection of LC3 and p62/SQSTM1 indicated that autophagy was inhibited, which correlated with increased <italic>SQSTM1</italic> and decreased <italic>BNIP3</italic> gene expression determined by qRT-PCR. Fluorescence microscopy and flow cytometry uncovered an accumulation of lysosomes. Similarly, transmission electron microscopy demonstrated the accumulation of autophagosomes confirming the ability of Lys05 to potentiate autophagy inhibition in H1299 cells. We report here for the first time that Lys05 could be utilized in combination with IR as a promising future strategy in the eradication of lung cancer cells.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Farhat, F S" uniqKey="Farhat F">F.S. Farhat</name></author><author><name sortKey="Houhou, W" uniqKey="Houhou W">W. Houhou</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yu, L" uniqKey="Yu L">L. Yu</name></author><author><name sortKey="Shang, Z F" uniqKey="Shang Z">Z.-F. Shang</name></author><author><name sortKey="Hsu, F M" uniqKey="Hsu F">F.-M. Hsu</name></author><author><name sortKey="Zhang, Z" uniqKey="Zhang Z">Z. Zhang</name></author><author><name sortKey="Tumati, V" uniqKey="Tumati V">V. 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Amaravadi</name><name sortKey="Bezrouk, Ales" sort="Bezrouk, Ales" uniqKey="Bezrouk A" first="Ales" last="Bezrouk">Ales Bezrouk</name><name sortKey="Cechakova, Lucie" sort="Cechakova, Lucie" uniqKey="Cechakova L" first="Lucie" last="Cechakova">Lucie Cechakova</name><name sortKey="Cizkova, Dana" sort="Cizkova, Dana" uniqKey="Cizkova D" first="Dana" last="Cizkova">Dana Cizkova</name><name sortKey="Jost, Petr" sort="Jost, Petr" uniqKey="Jost P" first="Petr" last="Jost">Petr Jost</name><name sortKey="Ondrej, Martin" sort="Ondrej, Martin" uniqKey="Ondrej M" first="Martin" last="Ondrej">Martin Ondrej</name><name sortKey="Pejchal, Jaroslav" sort="Pejchal, Jaroslav" uniqKey="Pejchal J" first="Jaroslav" last="Pejchal">Jaroslav Pejchal</name><name sortKey="Tichy, Ales" sort="Tichy, Ales" uniqKey="Tichy A" first="Ales" last="Tichy">Ales Tichy</name><name sortKey="Winkler, Jeffrey D" sort="Winkler, Jeffrey D" uniqKey="Winkler J" first="Jeffrey D." last="Winkler">Jeffrey D. Winkler</name></noCountry><country name="République tchèque"><noRegion><name sortKey="Pavlik, Vojtech" sort="Pavlik, Vojtech" uniqKey="Pavlik V" first="Vojtech" last="Pavlik">Vojtech Pavlik</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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