Gartanin induces autophagy through JNK activation which extenuates caspase-dependent apoptosis

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dc.contributor.authorMun-Ock Kim-
dc.contributor.authorHyun Sun Lee-
dc.contributor.authorY W Chin-
dc.contributor.authorD O Moon-
dc.contributor.authorJong Seog Ahn-
dc.date.accessioned2017-04-19T10:06:31Z-
dc.date.available2017-04-19T10:06:31Z-
dc.date.issued2015-
dc.identifier.issn1021-335X-
dc.identifier.uri10.3892/or.2015.3948ko
dc.identifier.urihttps://oak.kribb.re.kr/handle/201005/12662-
dc.description.abstractHepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. Development of novel agents to eradicate liver cancer cells is required for treatment of HCC. Gartanin, a xanthone-type compound isolated from mangosteen, is known to possess potent antioxidant, antiinflammatory, antifungal and antineoplastic properties. In the present study, we investigated the cytotoxic effect of gartanin on HCC and explored the cell death mechanism. We showed that gartanin induced both the extrinsic and intrinsic apoptotic pathways, which were interconnected by caspase-8, -9 and -3 activation. We also provided convincing evidence that gartanin induced autophagy in various cancer cells, as demonstrated by acridine orange staining of intracellular acidic vesicles, the degradation of p62, the conversion of LC3-I to LC3-II and GFP-LC3 punctate fluorescence. Additionally, gartanin induced the formation of typical autophagosomes and autolysosomes and enhanced the degradation rate of intracellular granule(s), including mitochondria. Notably, gartanin-mediated apoptotic cell death was further potentiated by pretreatment with autophagy inhibitors (3-methyladenine and bafilomycin A1) or small interfering RNAs against the autophagic genes (Atg5). These findings suggested that gartanin-mediated autophagic response protected against eventual cell death induced by gartanin. Moreover, gartanin treatment led to phosphorylation/activation of JNK and JNK-dependent phosphorylation of Bcl-2. Importantly, JNK inhibitor (SP600125) inhibited autophagy yet promoted gartanin-induced apoptosis, indicating a key requirement of the JNK-Bcl-2 pathway in the activation of autophagy by gartanin. Taken together, our data suggested that the JNK-Bcl-2 pathway was the critical regulator of gartanin-induced protective autophagy and a potential drug target for chemotherapeutic combination.-
dc.publisherSpandidos Publ Ltd-
dc.titleGartanin induces autophagy through JNK activation which extenuates caspase-dependent apoptosis-
dc.title.alternativeGartanin induces autophagy through JNK activation which extenuates caspase-dependent apoptosis-
dc.typeArticle-
dc.citation.titleOncology Reports-
dc.citation.number1-
dc.citation.endPage146-
dc.citation.startPage139-
dc.citation.volume34-
dc.contributor.affiliatedAuthorMun-Ock Kim-
dc.contributor.affiliatedAuthorHyun Sun Lee-
dc.contributor.affiliatedAuthorJong Seog Ahn-
dc.contributor.alternativeName김문옥-
dc.contributor.alternativeName이현선-
dc.contributor.alternativeName진영원-
dc.contributor.alternativeName문동오-
dc.contributor.alternativeName안종석-
dc.identifier.bibliographicCitationOncology Reports, vol. 34, no. 1, pp. 139-146-
dc.identifier.doi10.3892/or.2015.3948-
dc.subject.keywordApoptosis-
dc.subject.keywordAutophagy-
dc.subject.keywordGartanin-
dc.subject.keywordHepatocellular carcinoma-
dc.subject.keywordJNK-
dc.subject.localapoptosis-
dc.subject.localApoptosis-
dc.subject.localautophagy-
dc.subject.localAutophagy-
dc.subject.localGartanin-
dc.subject.localHepatocellular carcinomas-
dc.subject.localHepatocellular carcinoma (HCC)-
dc.subject.localHepatocellular carcinoma-
dc.subject.localhepatocellular carcinoma (HCC)-
dc.subject.localhepatocellular carcinoma-
dc.subject.localJNK-
dc.description.journalClassY-
Appears in Collections:
Ochang Branch Institute > Natural Product Research Center > 1. Journal Articles
Ochang Branch Institute > Chemical Biology Research Center > 1. Journal Articles
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