title: TEOA, a triterpenoid from Actinidia eriantha, induces autophagy in SW620 cells via endoplasmic reticulum stress and ROS-dependent mitophagy.
abstract: 2α,3α,24-Thrihydroxyurs-12-en-28-oicacid (TEOA), a pentacyclic triterpenoid, isolated from the roots of Actinidia eriantha, exhibits significant cytotoxicity against SW620, BGC-823, HepG-2, A549 and PC-3 cancer cells. In this study, we investigated the underlying molecular mechanism of the anticancer activity of TEOA in SW620 cells. We demonstrated that TEOA induced apoptosis through cleavage of caspase-9 and PARP in SW620 cells. In addition, evidence of TEOA-mediated autophagy included the induction of autophagolysosomes and activation of autophagic markers LC-3B and p62. Further analysis illustrated that TEOA promoted the phosphorylation of PERK and elF2α, followed by up-regulation of the downstream protein CHOP, suggesting the involvement of PERK/eIF2α/CHOP pathway and ER stress in TEOA-induced autophagy in SW620 cells. Meanwhile, TEOA-mediated PINK1, Parkin, ubiquitin and p62 activation revealed that TEOA induced specific autophagy-mitophagy in SW620 cells. Additionally, an antioxidant NAC attenuated the TEOA-induced mitophagy, indicating that TEOA triggers mitophagy via a ROS-dependent pathway. Collectively, our findings revealed a novel cellular mechanism of TEOA in the colon cancer cell line SW620, thus providing a molecular basis for developing TEOA into an anti-tumor candidate.
authors.affiliation: Institute of Biomedical Engineering, College of Biomedical Engineering & Instrument Science, Zhejiang University, Hangzhou, China.
authors.forename: Dandan
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Institute of Biomedical Engineering, College of Biomedical Engineering & Instrument Science, Zhejiang University, Hangzhou, China.
authors.forename: Cuixia
authors.initials: C
authors.lastname: Gao
authors.affiliation: Institute of Biomedical Engineering, College of Biomedical Engineering & Instrument Science, Zhejiang University, Hangzhou, China.
authors.forename: Ruyi
authors.initials: R
authors.lastname: Li
authors.affiliation: Institute of Biomedical Engineering, College of Biomedical Engineering & Instrument Science, Zhejiang University, Hangzhou, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Institute of Biomedical Engineering, College of Biomedical Engineering & Instrument Science, Zhejiang University, Hangzhou, China. tjk@zju.edu.cn.|Zhejiang-Malaysia Joint Research Center for Traditional Medicine, Zhejiang University, Hangzhou, China. tjk@zju.edu.cn.
authors.forename: Jingkui
authors.initials: J
authors.lastname: Tian
mesh_terms: D029042:Actinidia / Q000737:chemistry*; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D006801:Humans; D015394:Molecular Structure; D018517:Plant Roots / Q000737:chemistry; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014315:Triterpenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: C584867:2alpha,3alpha,24-trihydroxyurs-12-en-28-oic acid; D000972:Antineoplastic Agents, Phytogenic; D017382:Reactive Oxygen Species; D014315:Triterpenes
keywords: Actinidia eriantha root; Autophagy; ER stress; Mitophagy; SW620; TEOA