title: Quercetin induces protective autophagy and apoptosis through ER stress via the p-STAT3/Bcl-2 axis in ovarian cancer.
abstract: Quercetin (3,3',4',5,7-pentahydroxyflavone, Qu) is a promising cancer chemo-preventive agent for various cancers because it inhibits disease progression and promotes apoptotic cell death. In our previous study, we demonstrated that Qu could evoke ER stress to enhance drug cytotoxicity in ovarian cancer (OC). However, Qu-induced ER stress in OC is still poorly understood. Here, we demonstrated that Qu evoked ER stress to involve in mitochondria apoptosis pathway via the p-STAT3/Bcl-2 axis in OC cell lines and in primary OC cells. Unexpectedly, inhibition of ER stress did not reverse Qu-induced cell death. Further functional studies revealed that Qu-induced ER stress could activate protective autophagy concomitantly by activating the p-STAT3/Bcl-2 axis in this process. Moreover, the autophagy scavenger 3-MA was shown to enhance Qu's anticancer effects in an ovarian cancer mice xenograft model. These findings revealed a novel role of ER stress as a "double edge sword" participating in Qu-induced apoptosis of OC and might provide a new angle to consider in clinical studies of biological modifiers that may circumvent drug resistance in patients by targeting protective autophagy pathways.
authors.affiliation: Cancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, People's Republic of China.|Department of Medicinal Chemistry, School of Pharmacy, Hubei University of Chinese Medicine, Wuhan, Hubei, 430065, People's Republic of China.
authors.forename: Y
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Oncology, XiangYang Central Hospital, Hubei University of Arts and Science, Xiangyang, 441021, China.
authors.forename: W
authors.initials: W
authors.lastname: Gong
authors.affiliation: Cancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, People's Republic of China.
authors.forename: Z Y
authors.initials: ZY
authors.lastname: Yang
authors.affiliation: Cancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, People's Republic of China.
authors.forename: X S
authors.initials: XS
authors.lastname: Zhou
authors.affiliation: Cancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, People's Republic of China.
authors.forename: C
authors.initials: C
authors.lastname: Gong
authors.affiliation: Cancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, People's Republic of China.
authors.forename: T R
authors.initials: TR
authors.lastname: Zhang
authors.affiliation: Cancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, People's Republic of China.
authors.forename: X
authors.initials: X
authors.lastname: Wei
authors.affiliation: Cancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, People's Republic of China.
authors.forename: D
authors.initials: D
authors.lastname: Ma
authors.affiliation: Nuerosurgery Department, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, People's Republic of China. yeyuanbei@hotmail.com.
authors.forename: F
authors.initials: F
authors.lastname: Ye
authors.affiliation: Cancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, People's Republic of China. qlgao@tjh.tjmu.edu.cn.
authors.forename: Q L
authors.initials: QL
authors.lastname: Gao
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D001343:Autophagy / Q000187:drug effects* / Q000502:physiology; D045744:Cell Line, Tumor; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D005260:Female; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D008819:Mice, Nude; D016513:Mice, SCID; D009363:Neoplasm Proteins / Q000502:physiology*; D010051:Ovarian Neoplasms / Q000473:pathology*; D011794:Quercetin / Q000494:pharmacology* / Q000627:therapeutic use; D034741:RNA, Small Interfering / Q000235:genetics; D011897:Random Allocation; D050796:STAT3 Transcription Factor / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013047:Specific Pathogen-Free Organisms; D013655:Taurochenodeoxycholic Acid / Q000494:pharmacology; D014410:Tumor Stem Cell Assay; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D009363:Neoplasm Proteins; D034741:RNA, Small Interfering; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C025946:3-methyladenine; D013655:Taurochenodeoxycholic Acid; C031655:ursodoxicoltaurine; D011794:Quercetin; D000225:Adenine
keywords: Autophagy; ER stress; Ovarian cancer; Qu; p-STAT3/Bcl-2 axis