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Dandan Zhang,Cuixia Gao,Ruyi Li,Lin Zhang,Jingkui Tian 대한약학회 2017 Archives of Pharmacal Research Vol.40 No.5
2a,3a,24-Thrihydroxyurs-12-en-28-oicacid (TEOA),a pentacyclic triterpenoid, isolated from the roots of Actinidiaeriantha, exhibits significant cytotoxicity against SW620, BGC-823, HepG-2, A549 and PC-3 cancer cells. In this study, weinvestigated the underlying molecular mechanism of the anticanceractivity of TEOA in SW620 cells.We demonstrated thatTEOA induced apoptosis through cleavage of caspase-9 andPARP in SW620 cells. In addition, evidence of TEOA-mediatedautophagy included the induction of autophagolysosomesand activation of autophagic markers LC-3B and p62. Furtheranalysis illustrated that TEOA promoted the phosphorylation ofPERK and elF2a, followed by up-regulation of the downstreamprotein CHOP, suggesting the involvement of PERK/eIF2a/CHOP pathway and ER stress in TEOA-induced autophagy inSW620 cells. Meanwhile, TEOA-mediated PINK1, Parkin,ubiquitin and p62 activation revealed that TEOA inducedspecific autophagy-mitophagy in SW620 cells. Additionally, anantioxidant NAC attenuated the TEOA-induced mitophagy,indicating that TEOA triggers mitophagy via a ROS-dependentpathway. Collectively, our findings revealed a novel cellularmechanism of TEOA in the colon cancer cell line SW620, thusproviding a molecular basis for developing TEOA into an antitumorcandidate.