Obatoclax induces Beclin 1‐ and ATG5‐dependent apoptosis and autophagy in adenoid cystic carcinoma cells
Identifieur interne : 000F34 ( Main/Exploration ); précédent : 000F33; suivant : 000F35Obatoclax induces Beclin 1‐ and ATG5‐dependent apoptosis and autophagy in adenoid cystic carcinoma cells
Auteurs : L-Z Liang [République populaire de Chine] ; B. Ma [République populaire de Chine] ; Y-J Liang [République populaire de Chine] ; H-C Liu [République populaire de Chine] ; T-H Zhang [République populaire de Chine] ; G-S Zheng [République populaire de Chine] ; Y-X Su [République populaire de Chine, Hong Kong] ; G-Q Liao [République populaire de Chine, Hong Kong]Source :
- Oral Diseases [ 1354-523X ] ; 2015-05.
Abstract
Objectives: Adenoid cystic carcinoma (ACC) is one of the most common salivary gland cancers. The prognosis of adenoid cystic carcinoma is poor for its high frequency of distant metastases and insensitivity to chemotherapy or molecular therapies. This study investigated the effect of Obatoclax on adenoid cystic carcinoma cells and its cytotoxic mechanism. Methods: Western blot, transmission electron microscopy, and pEGFP‐LC3 plasmids transfection were carried out to detect autophagy in ACC cells treated with Obatoclax. 3‐MA and RNA interference against Beclin 1 and ATG5 were used to inhibit autophagy. Then we used Western blot and Hochest 33342 staining for apoptosis assessment. Finally, cell viability was assessed by MTT assay. Results: We found that Obatoclax induced cytoprotective autophagy which depended on ATG5 and partly on Beclin 1 in adenoid cystic carcinoma cells. Furthermore, pharmacologically inhibiting Obatoclax‐induced autophagy promoted apoptosis. Downregulation of Beclin 1 or ATG5 attenuated the cytotoxicity of Obatoclax by suppressing both autophagy and apoptosis. Finally, when apoptosis was pharmacologically inhibited, autophagic cell death was initiated in adenoid cystic carcinoma cells treated with Obatoclax. Conclusion: In summary, Beclin 1 and ATG5 play important roles in regulating both Obatoclax‐induced autophagy and apoptosis in adenoid cystic carcinoma.
Url:
DOI: 10.1111/odi.12305
Affiliations:
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Ma</name></author><author><name sortKey="Liang, Y" sort="Liang, Y" uniqKey="Liang Y" first="Y-J" last="Liang">Y-J Liang</name></author><author><name sortKey="Liu, H" sort="Liu, H" uniqKey="Liu H" first="H-C" last="Liu">H-C Liu</name></author><author><name sortKey="Zhang, T" sort="Zhang, T" uniqKey="Zhang T" first="T-H" last="Zhang">T-H Zhang</name></author><author><name sortKey="Zheng, G" sort="Zheng, G" uniqKey="Zheng G" first="G-S" last="Zheng">G-S Zheng</name></author><author><name sortKey="Su, Y" sort="Su, Y" uniqKey="Su Y" first="Y-X" last="Su">Y-X Su</name></author><author><name sortKey="Liao, G" sort="Liao, G" uniqKey="Liao G" first="G-Q" last="Liao">G-Q Liao</name></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:8A36B674E7AA3BFA6BBD4503EAC386E15902ADBD</idno><date when="2015" year="2015">2015</date><idno type="doi">10.1111/odi.12305</idno><idno type="url">https://api.istex.fr/ark:/67375/WNG-117NQH1P-Z/fulltext.pdf</idno><idno type="wicri:Area/Istex/Corpus">002392</idno><idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Corpus" wicri:corpus="ISTEX">002392</idno><idno type="wicri:Area/Istex/Curation">002392</idno><idno type="wicri:Area/Istex/Checkpoint">000079</idno><idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Checkpoint">000079</idno><idno type="wicri:doubleKey">1354-523X:2015:Liang L:obatoclax:induces:beclin</idno><idno type="wicri:Area/Main/Merge">000F35</idno><idno type="wicri:Area/Main/Curation">000F34</idno><idno type="wicri:Area/Main/Exploration">000F34</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main">Obatoclax induces Beclin 1‐ and ATG5‐dependent apoptosis and autophagy in adenoid cystic carcinoma cells</title><author><name sortKey="Liang, L" sort="Liang, L" uniqKey="Liang L" first="L-Z" last="Liang">L-Z Liang</name><affiliation wicri:level="1"><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Oral and Maxillofacial Surgery, Fifth Affiliated Hospital of Sun Yat‐sen University, Zhuhai</wicri:regionArea><wicri:noRegion>Zhuhai</wicri:noRegion></affiliation></author><author><name sortKey="Ma, B" sort="Ma, B" uniqKey="Ma B" first="B" last="Ma">B. Ma</name><affiliation wicri:level="1"><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Stomatology, Shanxi Academy of Medical Sciences, Shanxi Dayi Hospital, Taiyuan</wicri:regionArea><wicri:noRegion>Taiyuan</wicri:noRegion></affiliation></author><author><name sortKey="Liang, Y" sort="Liang, Y" uniqKey="Liang Y" first="Y-J" last="Liang">Y-J Liang</name><affiliation wicri:level="3"><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Oral and Maxillofacial Surgery, Guanghua School of Stomatology, Sun Yat‐Sen University, Guangzhou</wicri:regionArea><placeName><settlement type="city">Jiangmen</settlement><region type="province">Guangdong</region></placeName></affiliation></author><author><name sortKey="Liu, H" sort="Liu, H" uniqKey="Liu H" first="H-C" last="Liu">H-C Liu</name><affiliation wicri:level="3"><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Oral and Maxillofacial Surgery, Guanghua School of Stomatology, Sun Yat‐Sen University, Guangzhou</wicri:regionArea><placeName><settlement type="city">Jiangmen</settlement><region type="province">Guangdong</region></placeName></affiliation></author><author><name sortKey="Zhang, T" sort="Zhang, T" uniqKey="Zhang T" first="T-H" last="Zhang">T-H Zhang</name><affiliation wicri:level="1"><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Stomatology, Affiliated Zhongshan Hospital, Sun Yat‐sen University, Zhongshan</wicri:regionArea><wicri:noRegion>Zhongshan</wicri:noRegion></affiliation></author><author><name sortKey="Zheng, G" sort="Zheng, G" uniqKey="Zheng G" first="G-S" last="Zheng">G-S Zheng</name><affiliation wicri:level="3"><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Oral and Maxillofacial Surgery, Guanghua School of Stomatology, Sun Yat‐Sen University, Guangzhou</wicri:regionArea><placeName><settlement type="city">Jiangmen</settlement><region type="province">Guangdong</region></placeName></affiliation></author><author><name sortKey="Su, Y" sort="Su, Y" uniqKey="Su Y" first="Y-X" last="Su">Y-X Su</name><affiliation wicri:level="3"><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Oral and Maxillofacial Surgery, Guanghua School of Stomatology, Sun Yat‐Sen University, Guangzhou</wicri:regionArea><placeName><settlement type="city">Jiangmen</settlement><region type="province">Guangdong</region></placeName></affiliation><affiliation wicri:level="1"><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Discipline of Oral & Maxillofacial Surgery, Faculty of Dentistry, the University of Hong Kong, Hong Kong</wicri:regionArea><wicri:noRegion>Hong Kong</wicri:noRegion></affiliation><affiliation></affiliation><affiliation wicri:level="1"><country wicri:rule="url">Hong Kong</country></affiliation></author><author><name sortKey="Liao, G" sort="Liao, G" uniqKey="Liao G" first="G-Q" last="Liao">G-Q Liao</name><affiliation wicri:level="3"><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Oral and Maxillofacial Surgery, Guanghua School of Stomatology, Sun Yat‐Sen University, Guangzhou</wicri:regionArea><placeName><settlement type="city">Jiangmen</settlement><region type="province">Guangdong</region></placeName></affiliation><affiliation></affiliation><affiliation wicri:level="1"><country wicri:rule="url">Hong Kong</country></affiliation></author></analytic><monogr></monogr><series><title level="j" type="main">Oral Diseases</title><title level="j" type="alt">ORAL DISEASES</title><idno type="ISSN">1354-523X</idno><idno type="eISSN">1601-0825</idno><imprint><biblScope unit="vol">21</biblScope><biblScope unit="issue">4</biblScope><biblScope unit="page" from="470">470</biblScope><biblScope unit="page" to="477">477</biblScope><biblScope unit="page-count">8</biblScope><date type="published" when="2015-05">2015-05</date></imprint><idno type="ISSN">1354-523X</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">1354-523X</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract">Objectives: Adenoid cystic carcinoma (ACC) is one of the most common salivary gland cancers. The prognosis of adenoid cystic carcinoma is poor for its high frequency of distant metastases and insensitivity to chemotherapy or molecular therapies. This study investigated the effect of Obatoclax on adenoid cystic carcinoma cells and its cytotoxic mechanism. Methods: Western blot, transmission electron microscopy, and pEGFP‐LC3 plasmids transfection were carried out to detect autophagy in ACC cells treated with Obatoclax. 3‐MA and RNA interference against Beclin 1 and ATG5 were used to inhibit autophagy. Then we used Western blot and Hochest 33342 staining for apoptosis assessment. Finally, cell viability was assessed by MTT assay. Results: We found that Obatoclax induced cytoprotective autophagy which depended on ATG5 and partly on Beclin 1 in adenoid cystic carcinoma cells. Furthermore, pharmacologically inhibiting Obatoclax‐induced autophagy promoted apoptosis. Downregulation of Beclin 1 or ATG5 attenuated the cytotoxicity of Obatoclax by suppressing both autophagy and apoptosis. Finally, when apoptosis was pharmacologically inhibited, autophagic cell death was initiated in adenoid cystic carcinoma cells treated with Obatoclax. Conclusion: In summary, Beclin 1 and ATG5 play important roles in regulating both Obatoclax‐induced autophagy and apoptosis in adenoid cystic carcinoma.</div></front></TEI><affiliations><list><country><li>Hong Kong</li><li>République populaire de Chine</li></country><region><li>Guangdong</li></region><settlement><li>Jiangmen</li></settlement></list><tree><country name="République populaire de Chine"><noRegion><name sortKey="Liang, L" sort="Liang, L" uniqKey="Liang L" first="L-Z" last="Liang">L-Z Liang</name></noRegion><name sortKey="Liang, Y" sort="Liang, Y" uniqKey="Liang Y" first="Y-J" last="Liang">Y-J Liang</name><name sortKey="Liao, G" sort="Liao, G" uniqKey="Liao G" first="G-Q" last="Liao">G-Q Liao</name><name sortKey="Liu, H" sort="Liu, H" uniqKey="Liu H" first="H-C" last="Liu">H-C Liu</name><name sortKey="Ma, B" sort="Ma, B" uniqKey="Ma B" first="B" last="Ma">B. Ma</name><name sortKey="Su, Y" sort="Su, Y" uniqKey="Su Y" first="Y-X" last="Su">Y-X Su</name><name sortKey="Su, Y" sort="Su, Y" uniqKey="Su Y" first="Y-X" last="Su">Y-X Su</name><name sortKey="Zhang, T" sort="Zhang, T" uniqKey="Zhang T" first="T-H" last="Zhang">T-H Zhang</name><name sortKey="Zheng, G" sort="Zheng, G" uniqKey="Zheng G" first="G-S" last="Zheng">G-S Zheng</name></country><country name="Hong Kong"><noRegion><name sortKey="Su, Y" sort="Su, Y" uniqKey="Su Y" first="Y-X" last="Su">Y-X Su</name></noRegion><name sortKey="Liao, G" sort="Liao, G" uniqKey="Liao G" first="G-Q" last="Liao">G-Q Liao</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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