Identification of Chaetocin as a Potent non-ROS-mediated Anticancer Drug Candidate for Gastric Cancer
Identifieur interne : 000762 ( Main/Exploration ); précédent : 000761; suivant : 000763Identification of Chaetocin as a Potent non-ROS-mediated Anticancer Drug Candidate for Gastric Cancer
Auteurs : Xinwen Liao [République populaire de Chine] ; Yaqiong Fan [République populaire de Chine] ; Jihuan Hou [République populaire de Chine] ; Xiong Chen [République populaire de Chine] ; Xiaolin Xu [République populaire de Chine] ; Yifan Yang [République populaire de Chine] ; Jinying Shen [République populaire de Chine] ; Panying Mi [République populaire de Chine] ; Xiaohua Huang [République populaire de Chine] ; Wenqing Zhang [République populaire de Chine] ; Hanwei Cao [République populaire de Chine] ; Xiaoting Hong [République populaire de Chine] ; Tianhui Hu [République populaire de Chine] ; Yan-Yan Zhan [République populaire de Chine]Source :
- Journal of Cancer [ 1837-9664 ] ; 2019.
Abstract
Chaetocin, a natural product extracted from Chaetomium species, possesses anticancer effects in several kinds of tumors. However, it remains unclear whether the potential indication for chaetocin could also include human gastric cancer. We found here that chaetocin induced caspase-dependent and -independent apoptosis in human gastric cancer cell lines, which greatly depended on BID-mediated AIF translocation. Despite not increasing the intercellular ROS levels in gastric cancer cells, chaetocin did cause a reduction in mitochondrial membrane potential probably through its regulation on the expression of Bcl-2 and BAX. Chaetocin could also induce autophagy in gastric cancer cells; blocking autophagy by chloroquine enhanced the cytotoxicity of chaetocin. Chaetocin was further found to suppress the growth of gastric cancer xenograft in nude mice. Therefore, our study provides first evidence that chaetocin has an anticancer efficacy against gastric cancer and the combined use of chaetocin with autophagy inhibitors may enhance the therapeutic effect for gastric cancer. As chronic and exorbitant ROS levels instigate drug resistance, chaetocin, which eradicates gastric cancer cells without increasing ROS levels, may initiate a new line of non-ROS-mediated anti-tumor strategy.
Url:
DOI: 10.7150/jca.32803
PubMed: 31333785
PubMed Central: 6636309
Affiliations:
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China</nlm:aff><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>Cancer Research Center, School of Medicine, Xiamen University, Xiamen 361102, Fujian</wicri:regionArea><wicri:noRegion>Fujian</wicri:noRegion></affiliation></author><author><name sortKey="Fan, Yaqiong" sort="Fan, Yaqiong" uniqKey="Fan Y" first="Yaqiong" last="Fan">Yaqiong Fan</name><affiliation wicri:level="1"><nlm:aff id="A1">Cancer Research Center, School of Medicine, Xiamen University, Xiamen 361102, Fujian, P.R. China</nlm:aff><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>Cancer Research Center, School of Medicine, Xiamen University, Xiamen 361102, Fujian</wicri:regionArea><wicri:noRegion>Fujian</wicri:noRegion></affiliation></author><author><name sortKey="Hou, Jihuan" sort="Hou, Jihuan" uniqKey="Hou J" first="Jihuan" last="Hou">Jihuan Hou</name><affiliation wicri:level="1"><nlm:aff id="A1">Cancer Research Center, School of Medicine, Xiamen University, Xiamen 361102, Fujian, P.R. 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China</nlm:aff><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>Cancer Research Center, School of Medicine, Xiamen University, Xiamen 361102, Fujian</wicri:regionArea><wicri:noRegion>Fujian</wicri:noRegion></affiliation></author><author><name sortKey="Yang, Yifan" sort="Yang, Yifan" uniqKey="Yang Y" first="Yifan" last="Yang">Yifan Yang</name><affiliation wicri:level="1"><nlm:aff id="A1">Cancer Research Center, School of Medicine, Xiamen University, Xiamen 361102, Fujian, P.R. China</nlm:aff><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>Cancer Research Center, School of Medicine, Xiamen University, Xiamen 361102, Fujian</wicri:regionArea><wicri:noRegion>Fujian</wicri:noRegion></affiliation></author><author><name sortKey="Shen, Jinying" sort="Shen, Jinying" uniqKey="Shen J" first="Jinying" last="Shen">Jinying Shen</name><affiliation wicri:level="1"><nlm:aff id="A1">Cancer Research Center, School of Medicine, Xiamen University, Xiamen 361102, Fujian, P.R. China</nlm:aff><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>Cancer Research Center, School of Medicine, Xiamen University, Xiamen 361102, Fujian</wicri:regionArea><wicri:noRegion>Fujian</wicri:noRegion></affiliation></author><author><name sortKey="Mi, Panying" sort="Mi, Panying" uniqKey="Mi P" first="Panying" last="Mi">Panying Mi</name><affiliation wicri:level="1"><nlm:aff id="A1">Cancer Research Center, School of Medicine, Xiamen University, Xiamen 361102, Fujian, P.R. China</nlm:aff><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>Cancer Research Center, School of Medicine, Xiamen University, Xiamen 361102, Fujian</wicri:regionArea><wicri:noRegion>Fujian</wicri:noRegion></affiliation></author><author><name sortKey="Huang, Xiaohua" sort="Huang, Xiaohua" uniqKey="Huang X" first="Xiaohua" last="Huang">Xiaohua Huang</name><affiliation wicri:level="1"><nlm:aff id="A2">Department of Basic Medicine, School of Medicine, Xiamen University, Xiamen 361102, Fujian, P.R. China</nlm:aff><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>Department of Basic Medicine, School of Medicine, Xiamen University, Xiamen 361102, Fujian</wicri:regionArea><wicri:noRegion>Fujian</wicri:noRegion></affiliation></author><author><name sortKey="Zhang, Wenqing" sort="Zhang, Wenqing" uniqKey="Zhang W" first="Wenqing" last="Zhang">Wenqing Zhang</name><affiliation wicri:level="1"><nlm:aff id="A1">Cancer Research Center, School of Medicine, Xiamen University, Xiamen 361102, Fujian, P.R. China</nlm:aff><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>Cancer Research Center, School of Medicine, Xiamen University, Xiamen 361102, Fujian</wicri:regionArea><wicri:noRegion>Fujian</wicri:noRegion></affiliation></author><author><name sortKey="Cao, Hanwei" sort="Cao, Hanwei" uniqKey="Cao H" first="Hanwei" last="Cao">Hanwei Cao</name><affiliation wicri:level="1"><nlm:aff id="A1">Cancer Research Center, School of Medicine, Xiamen University, Xiamen 361102, Fujian, P.R. China</nlm:aff><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>Cancer Research Center, School of Medicine, Xiamen University, Xiamen 361102, Fujian</wicri:regionArea><wicri:noRegion>Fujian</wicri:noRegion></affiliation></author><author><name sortKey="Hong, Xiaoting" sort="Hong, Xiaoting" uniqKey="Hong X" first="Xiaoting" last="Hong">Xiaoting Hong</name><affiliation wicri:level="1"><nlm:aff id="A2">Department of Basic Medicine, School of Medicine, Xiamen University, Xiamen 361102, Fujian, P.R. China</nlm:aff><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>Department of Basic Medicine, School of Medicine, Xiamen University, Xiamen 361102, Fujian</wicri:regionArea><wicri:noRegion>Fujian</wicri:noRegion></affiliation></author><author><name sortKey="Hu, Tianhui" sort="Hu, Tianhui" uniqKey="Hu T" first="Tianhui" last="Hu">Tianhui Hu</name><affiliation wicri:level="1"><nlm:aff id="A1">Cancer Research Center, School of Medicine, Xiamen University, Xiamen 361102, Fujian, P.R. China</nlm:aff><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>Cancer Research Center, School of Medicine, Xiamen University, Xiamen 361102, Fujian</wicri:regionArea><wicri:noRegion>Fujian</wicri:noRegion></affiliation></author><author><name sortKey="Zhan, Yan Yan" sort="Zhan, Yan Yan" uniqKey="Zhan Y" first="Yan-Yan" last="Zhan">Yan-Yan Zhan</name><affiliation wicri:level="1"><nlm:aff id="A1">Cancer Research Center, School of Medicine, Xiamen University, Xiamen 361102, Fujian, P.R. China</nlm:aff><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>Cancer Research Center, School of Medicine, Xiamen University, Xiamen 361102, Fujian</wicri:regionArea><wicri:noRegion>Fujian</wicri:noRegion></affiliation></author></analytic><series><title level="j">Journal of Cancer</title><idno type="eISSN">1837-9664</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>Chaetocin, a natural product extracted from Chaetomium species, possesses anticancer effects in several kinds of tumors. However, it remains unclear whether the potential indication for chaetocin could also include human gastric cancer. We found here that chaetocin induced caspase-dependent and -independent apoptosis in human gastric cancer cell lines, which greatly depended on BID-mediated AIF translocation. Despite not increasing the intercellular ROS levels in gastric cancer cells, chaetocin did cause a reduction in mitochondrial membrane potential probably through its regulation on the expression of Bcl-2 and BAX. Chaetocin could also induce autophagy in gastric cancer cells; blocking autophagy by chloroquine enhanced the cytotoxicity of chaetocin. Chaetocin was further found to suppress the growth of gastric cancer xenograft in nude mice. Therefore, our study provides first evidence that chaetocin has an anticancer efficacy against gastric cancer and the combined use of chaetocin with autophagy inhibitors may enhance the therapeutic effect for gastric cancer. As chronic and exorbitant ROS levels instigate drug resistance, chaetocin, which eradicates gastric cancer cells without increasing ROS levels, may initiate a new line of non-ROS-mediated anti-tumor strategy.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Ferro, A" uniqKey="Ferro A">A Ferro</name></author><author><name sortKey="Peleteiro, B" uniqKey="Peleteiro B">B Peleteiro</name></author><author><name sortKey="Malvezzi, M" uniqKey="Malvezzi M">M Malvezzi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Macdonald, Js" uniqKey="Macdonald J">JS Macdonald</name></author><author><name sortKey="Smalley, Sr" uniqKey="Smalley S">SR Smalley</name></author><author><name sortKey="Benedetti, J" uniqKey="Benedetti J">J Benedetti</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="De Angelis, R" uniqKey="De Angelis R">R De Angelis</name></author><author><name sortKey="Sant, 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sort="Cao, Hanwei" uniqKey="Cao H" first="Hanwei" last="Cao">Hanwei Cao</name><name sortKey="Chen, Xiong" sort="Chen, Xiong" uniqKey="Chen X" first="Xiong" last="Chen">Xiong Chen</name><name sortKey="Fan, Yaqiong" sort="Fan, Yaqiong" uniqKey="Fan Y" first="Yaqiong" last="Fan">Yaqiong Fan</name><name sortKey="Hong, Xiaoting" sort="Hong, Xiaoting" uniqKey="Hong X" first="Xiaoting" last="Hong">Xiaoting Hong</name><name sortKey="Hou, Jihuan" sort="Hou, Jihuan" uniqKey="Hou J" first="Jihuan" last="Hou">Jihuan Hou</name><name sortKey="Hu, Tianhui" sort="Hu, Tianhui" uniqKey="Hu T" first="Tianhui" last="Hu">Tianhui Hu</name><name sortKey="Huang, Xiaohua" sort="Huang, Xiaohua" uniqKey="Huang X" first="Xiaohua" last="Huang">Xiaohua Huang</name><name sortKey="Mi, Panying" sort="Mi, Panying" uniqKey="Mi P" first="Panying" last="Mi">Panying Mi</name><name sortKey="Shen, Jinying" sort="Shen, Jinying" uniqKey="Shen J" first="Jinying" last="Shen">Jinying Shen</name><name sortKey="Xu, Xiaolin" sort="Xu, Xiaolin" uniqKey="Xu X" first="Xiaolin" last="Xu">Xiaolin Xu</name><name sortKey="Yang, Yifan" sort="Yang, Yifan" uniqKey="Yang Y" first="Yifan" last="Yang">Yifan Yang</name><name sortKey="Zhan, Yan Yan" sort="Zhan, Yan Yan" uniqKey="Zhan Y" first="Yan-Yan" last="Zhan">Yan-Yan Zhan</name><name sortKey="Zhang, Wenqing" sort="Zhang, Wenqing" uniqKey="Zhang W" first="Wenqing" last="Zhang">Wenqing Zhang</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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