N-Methylparoxetine Blocked Autophagic Flux and Induced Apoptosis by Activating ROS-MAPK Pathway in Non-Small Cell Lung Cancer Cells
Identifieur interne : 000B59 ( Main/Exploration ); précédent : 000B58; suivant : 000B60N-Methylparoxetine Blocked Autophagic Flux and Induced Apoptosis by Activating ROS-MAPK Pathway in Non-Small Cell Lung Cancer Cells
Auteurs : Kun Wang [République populaire de Chine] ; Bonan Chen [République populaire de Chine] ; Ting Yin [République populaire de Chine] ; Yujuan Zhan [République populaire de Chine] ; Yuhua Lu [République populaire de Chine] ; Yilin Zhang [République populaire de Chine] ; Jiawei Chen [République populaire de Chine] ; Weijie Wu [République populaire de Chine] ; Shikun Zhou [République populaire de Chine] ; Wenli Mao [République populaire de Chine] ; Yuhui Tan [République populaire de Chine] ; Biaoyan Du [République populaire de Chine] ; Xiaodong Liu [République populaire de Chine] ; Hiuting Idy Ho [République populaire de Chine] ; Jianyong Xiao [République populaire de Chine]Source :
- International Journal of Molecular Sciences [ 1422-0067 ] ; 2019.
Abstract
The main mechanistic function of most chemotherapeutic drugs is mediated by inducing mitochondria-dependent apoptosis. Tumor cells usually respond to upregulate autophagy to eliminate impaired mitochondria for survival. Hypothetically, inhibiting autophagy might promote mitochondria-dependent apoptosis, thus enhancing the efficacy of chemotherapeutic therapies. We previously identified
Url:
DOI: 10.3390/ijms20143415
PubMed: 31336784
PubMed Central: 6678301
Affiliations:
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510006, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Biochemistry, Guangzhou University of Chinese Medicine, Guangzhou 510006</wicri:regionArea><placeName><settlement type="city">Jiangmen</settlement><region type="province">Guangdong</region></placeName></affiliation></author><author><name sortKey="Lu, Yuhua" sort="Lu, Yuhua" uniqKey="Lu Y" first="Yuhua" last="Lu">Yuhua Lu</name><affiliation wicri:level="1"><nlm:aff id="af2-ijms-20-03415">Department of Pathology, Guangzhou University of Chinese Medicine, Guangzhou 510006, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Pathology, Guangzhou University of Chinese Medicine, Guangzhou 510006</wicri:regionArea><placeName><settlement type="city">Jiangmen</settlement><region type="province">Guangdong</region></placeName></affiliation></author><author><name sortKey="Zhang, Yilin" sort="Zhang, Yilin" uniqKey="Zhang Y" 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Center of Integrative Medicine, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006</wicri:regionArea><placeName><settlement type="city">Jiangmen</settlement><region type="province">Guangdong</region></placeName></affiliation><affiliation wicri:level="1"><nlm:aff id="af2-ijms-20-03415">Department of Pathology, Guangzhou University of Chinese Medicine, Guangzhou 510006, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Pathology, Guangzhou University of Chinese Medicine, Guangzhou 510006</wicri:regionArea><placeName><settlement type="city">Jiangmen</settlement><region type="province">Guangdong</region></placeName></affiliation></author><author><name sortKey="Chen, Bonan" sort="Chen, Bonan" uniqKey="Chen B" first="Bonan" last="Chen">Bonan Chen</name><affiliation wicri:level="1"><nlm:aff id="af1-ijms-20-03415">Research Center of Integrative Medicine, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Research Center of Integrative Medicine, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006</wicri:regionArea><placeName><settlement type="city">Jiangmen</settlement><region type="province">Guangdong</region></placeName></affiliation><affiliation wicri:level="1"><nlm:aff id="af3-ijms-20-03415">Department of Biochemistry, Guangzhou University of Chinese Medicine, Guangzhou 510006, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Biochemistry, Guangzhou University of Chinese Medicine, Guangzhou 510006</wicri:regionArea><placeName><settlement type="city">Jiangmen</settlement><region type="province">Guangdong</region></placeName></affiliation></author><author><name sortKey="Yin, Ting" sort="Yin, Ting" uniqKey="Yin T" first="Ting" last="Yin">Ting Yin</name><affiliation wicri:level="1"><nlm:aff id="af1-ijms-20-03415">Research Center of Integrative Medicine, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Research Center of Integrative Medicine, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006</wicri:regionArea><placeName><settlement type="city">Jiangmen</settlement><region type="province">Guangdong</region></placeName></affiliation><affiliation wicri:level="1"><nlm:aff id="af3-ijms-20-03415">Department of Biochemistry, Guangzhou University of Chinese Medicine, Guangzhou 510006, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Biochemistry, Guangzhou University of Chinese Medicine, Guangzhou 510006</wicri:regionArea><placeName><settlement type="city">Jiangmen</settlement><region type="province">Guangdong</region></placeName></affiliation></author><author><name sortKey="Zhan, Yujuan" sort="Zhan, Yujuan" uniqKey="Zhan Y" first="Yujuan" last="Zhan">Yujuan Zhan</name><affiliation wicri:level="1"><nlm:aff id="af3-ijms-20-03415">Department of Biochemistry, Guangzhou University of Chinese Medicine, Guangzhou 510006, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Biochemistry, Guangzhou University of Chinese Medicine, Guangzhou 510006</wicri:regionArea><placeName><settlement type="city">Jiangmen</settlement><region type="province">Guangdong</region></placeName></affiliation></author><author><name sortKey="Lu, Yuhua" sort="Lu, Yuhua" uniqKey="Lu Y" first="Yuhua" last="Lu">Yuhua Lu</name><affiliation wicri:level="1"><nlm:aff id="af2-ijms-20-03415">Department of Pathology, Guangzhou University of Chinese Medicine, Guangzhou 510006, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Pathology, Guangzhou University of Chinese Medicine, Guangzhou 510006</wicri:regionArea><placeName><settlement type="city">Jiangmen</settlement><region type="province">Guangdong</region></placeName></affiliation></author><author><name sortKey="Zhang, Yilin" sort="Zhang, Yilin" uniqKey="Zhang Y" first="Yilin" last="Zhang">Yilin Zhang</name><affiliation wicri:level="1"><nlm:aff id="af2-ijms-20-03415">Department of Pathology, Guangzhou University of Chinese Medicine, Guangzhou 510006, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Pathology, Guangzhou University of Chinese Medicine, Guangzhou 510006</wicri:regionArea><placeName><settlement type="city">Jiangmen</settlement><region type="province">Guangdong</region></placeName></affiliation></author><author><name sortKey="Chen, Jiawei" sort="Chen, Jiawei" uniqKey="Chen J" first="Jiawei" last="Chen">Jiawei Chen</name><affiliation wicri:level="1"><nlm:aff id="af3-ijms-20-03415">Department of Biochemistry, Guangzhou University of Chinese Medicine, Guangzhou 510006, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Biochemistry, Guangzhou University of Chinese Medicine, Guangzhou 510006</wicri:regionArea><placeName><settlement type="city">Jiangmen</settlement><region type="province">Guangdong</region></placeName></affiliation></author><author><name sortKey="Wu, Weijie" sort="Wu, Weijie" uniqKey="Wu W" first="Weijie" last="Wu">Weijie Wu</name><affiliation wicri:level="1"><nlm:aff id="af3-ijms-20-03415">Department of Biochemistry, Guangzhou University of Chinese Medicine, Guangzhou 510006, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Biochemistry, Guangzhou University of Chinese Medicine, Guangzhou 510006</wicri:regionArea><placeName><settlement type="city">Jiangmen</settlement><region type="province">Guangdong</region></placeName></affiliation></author><author><name sortKey="Zhou, Shikun" sort="Zhou, Shikun" uniqKey="Zhou S" first="Shikun" last="Zhou">Shikun Zhou</name><affiliation wicri:level="1"><nlm:aff id="af3-ijms-20-03415">Department of Biochemistry, Guangzhou University of Chinese Medicine, Guangzhou 510006, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Biochemistry, Guangzhou University of Chinese Medicine, Guangzhou 510006</wicri:regionArea><placeName><settlement type="city">Jiangmen</settlement><region type="province">Guangdong</region></placeName></affiliation></author><author><name sortKey="Mao, Wenli" sort="Mao, Wenli" uniqKey="Mao W" first="Wenli" last="Mao">Wenli Mao</name><affiliation wicri:level="1"><nlm:aff id="af1-ijms-20-03415">Research Center of Integrative Medicine, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Research Center of Integrative Medicine, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006</wicri:regionArea><placeName><settlement type="city">Jiangmen</settlement><region type="province">Guangdong</region></placeName></affiliation><affiliation wicri:level="1"><nlm:aff id="af2-ijms-20-03415">Department of Pathology, Guangzhou University of Chinese Medicine, Guangzhou 510006, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Pathology, Guangzhou University of Chinese Medicine, Guangzhou 510006</wicri:regionArea><placeName><settlement type="city">Jiangmen</settlement><region type="province">Guangdong</region></placeName></affiliation></author><author><name sortKey="Tan, Yuhui" sort="Tan, Yuhui" uniqKey="Tan Y" first="Yuhui" last="Tan">Yuhui Tan</name><affiliation wicri:level="1"><nlm:aff id="af3-ijms-20-03415">Department of Biochemistry, Guangzhou University of Chinese Medicine, Guangzhou 510006, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Biochemistry, Guangzhou University of Chinese Medicine, Guangzhou 510006</wicri:regionArea><placeName><settlement type="city">Jiangmen</settlement><region type="province">Guangdong</region></placeName></affiliation></author><author><name sortKey="Du, Biaoyan" sort="Du, Biaoyan" uniqKey="Du B" first="Biaoyan" last="Du">Biaoyan Du</name><affiliation wicri:level="1"><nlm:aff id="af2-ijms-20-03415">Department of Pathology, Guangzhou University of Chinese Medicine, Guangzhou 510006, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Pathology, Guangzhou University of Chinese Medicine, Guangzhou 510006</wicri:regionArea><placeName><settlement type="city">Jiangmen</settlement><region type="province">Guangdong</region></placeName></affiliation></author><author><name sortKey="Liu, Xiaodong" sort="Liu, Xiaodong" uniqKey="Liu X" first="Xiaodong" last="Liu">Xiaodong Liu</name><affiliation wicri:level="4"><nlm:aff id="af4-ijms-20-03415">Department of Anaesthesia and Intensive Care, The Chinese University of Hong Kong, Hong Kong SAR 999077, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Anaesthesia and Intensive Care, The Chinese University of Hong Kong, Hong Kong SAR 999077</wicri:regionArea><orgName type="university">Université chinoise de Hong Kong</orgName><placeName><settlement type="city">Sha Tin</settlement></placeName></affiliation></author><author><name sortKey="Ho, Hiuting Idy" sort="Ho, Hiuting Idy" uniqKey="Ho H" first="Hiuting Idy" last="Ho">Hiuting Idy Ho</name><affiliation wicri:level="4"><nlm:aff id="af4-ijms-20-03415">Department of Anaesthesia and Intensive Care, The Chinese University of Hong Kong, Hong Kong SAR 999077, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Anaesthesia and Intensive Care, The Chinese University of Hong Kong, Hong Kong SAR 999077</wicri:regionArea><orgName type="university">Université chinoise de Hong Kong</orgName><placeName><settlement type="city">Sha Tin</settlement></placeName></affiliation></author><author><name sortKey="Xiao, Jianyong" sort="Xiao, Jianyong" uniqKey="Xiao J" first="Jianyong" last="Xiao">Jianyong Xiao</name><affiliation wicri:level="1"><nlm:aff id="af1-ijms-20-03415">Research Center of Integrative Medicine, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Research Center of Integrative Medicine, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006</wicri:regionArea><placeName><settlement type="city">Jiangmen</settlement><region type="province">Guangdong</region></placeName></affiliation><affiliation wicri:level="1"><nlm:aff id="af3-ijms-20-03415">Department of Biochemistry, Guangzhou University of Chinese Medicine, Guangzhou 510006, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Biochemistry, Guangzhou University of Chinese Medicine, Guangzhou 510006</wicri:regionArea><placeName><settlement type="city">Jiangmen</settlement><region type="province">Guangdong</region></placeName></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>The main mechanistic function of most chemotherapeutic drugs is mediated by inducing mitochondria-dependent apoptosis. Tumor cells usually respond to upregulate autophagy to eliminate impaired mitochondria for survival. Hypothetically, inhibiting autophagy might promote mitochondria-dependent apoptosis, thus enhancing the efficacy of chemotherapeutic therapies. We previously identified <italic>N</italic>-methylparoxetine (NMP) as an inducer of mitochondrial fragmentation with subsequent apoptosis in non-small cell lung cancer (NSCLC) cells. We discovered that ROS was accumulated in NMP-treated NSCLC cells, followed by c-Jun <italic>N</italic>-terminal kinase (JNK) and p38 MAP kinase (p38) activation. This was reversed by the application of a reactive oxygen species (ROS) scavenger, <italic>N</italic>-acetylcysteine (NAC), leading to a reduction in apoptosis. Our data suggested that NMP induced apoptosis in NSCLC cells by activating mitogen-activated protein kinase (MAPK) pathway. We further speculated that the remarkable increase of ROS in NMP-treated NSCLC cells might result from an inhibition of autophagy. Our current data confirmed that NMP blocked autophagy flux at late stage wherein lysosomal acidification was inhibited. Taken together, this study demonstrated that NMP could exert dual apoptotic functions—mitochondria impairment and, concomitantly, autophagy inhibition. NMP-related excessive ROS accumulation induced apoptosis by activating the MAPK pathway in NSCLC cells.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Bray, F" uniqKey="Bray F">F. Bray</name></author><author><name sortKey="Ferlay, J" uniqKey="Ferlay J">J. Ferlay</name></author><author><name sortKey="Soerjomataram, I" uniqKey="Soerjomataram I">I. Soerjomataram</name></author><author><name sortKey="Siegel, R L" uniqKey="Siegel R">R.L. Siegel</name></author><author><name sortKey="Torre, L A" uniqKey="Torre L">L.A. 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Reed</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>République populaire de Chine</li></country><region><li>Guangdong</li></region><settlement><li>Jiangmen</li><li>Sha Tin</li></settlement><orgName><li>Université chinoise de Hong Kong</li></orgName></list><tree><country name="République populaire de Chine"><region name="Guangdong"><name sortKey="Wang, Kun" sort="Wang, Kun" uniqKey="Wang K" first="Kun" last="Wang">Kun Wang</name></region><name sortKey="Chen, Bonan" sort="Chen, Bonan" uniqKey="Chen B" first="Bonan" last="Chen">Bonan Chen</name><name sortKey="Chen, Bonan" sort="Chen, Bonan" uniqKey="Chen B" first="Bonan" last="Chen">Bonan Chen</name><name sortKey="Chen, Jiawei" sort="Chen, Jiawei" uniqKey="Chen J" first="Jiawei" last="Chen">Jiawei Chen</name><name sortKey="Du, Biaoyan" sort="Du, Biaoyan" uniqKey="Du B" first="Biaoyan" last="Du">Biaoyan Du</name><name sortKey="Ho, Hiuting Idy" sort="Ho, Hiuting Idy" uniqKey="Ho H" first="Hiuting Idy" last="Ho">Hiuting Idy Ho</name><name sortKey="Liu, Xiaodong" sort="Liu, Xiaodong" uniqKey="Liu X" first="Xiaodong" last="Liu">Xiaodong Liu</name><name sortKey="Lu, Yuhua" sort="Lu, Yuhua" uniqKey="Lu Y" first="Yuhua" last="Lu">Yuhua Lu</name><name sortKey="Mao, Wenli" sort="Mao, Wenli" uniqKey="Mao W" first="Wenli" last="Mao">Wenli Mao</name><name sortKey="Mao, Wenli" sort="Mao, Wenli" uniqKey="Mao W" first="Wenli" last="Mao">Wenli Mao</name><name sortKey="Tan, Yuhui" sort="Tan, Yuhui" uniqKey="Tan Y" first="Yuhui" last="Tan">Yuhui Tan</name><name sortKey="Wang, Kun" sort="Wang, Kun" uniqKey="Wang K" first="Kun" last="Wang">Kun Wang</name><name sortKey="Wu, Weijie" sort="Wu, Weijie" uniqKey="Wu W" first="Weijie" last="Wu">Weijie Wu</name><name sortKey="Xiao, Jianyong" sort="Xiao, Jianyong" uniqKey="Xiao J" first="Jianyong" last="Xiao">Jianyong Xiao</name><name sortKey="Xiao, Jianyong" sort="Xiao, Jianyong" uniqKey="Xiao J" first="Jianyong" last="Xiao">Jianyong Xiao</name><name sortKey="Yin, Ting" sort="Yin, Ting" uniqKey="Yin T" first="Ting" last="Yin">Ting Yin</name><name sortKey="Yin, Ting" sort="Yin, Ting" uniqKey="Yin T" first="Ting" last="Yin">Ting Yin</name><name sortKey="Zhan, Yujuan" sort="Zhan, Yujuan" uniqKey="Zhan Y" first="Yujuan" last="Zhan">Yujuan Zhan</name><name sortKey="Zhang, Yilin" sort="Zhang, Yilin" uniqKey="Zhang Y" first="Yilin" last="Zhang">Yilin Zhang</name><name sortKey="Zhou, Shikun" sort="Zhou, Shikun" uniqKey="Zhou S" first="Shikun" last="Zhou">Shikun Zhou</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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