title: YAP and 14-3-3γ are involved in HS-OA-induced growth inhibition of hepatocellular carcinoma cells: A novel mechanism for hydrogen sulfide releasing oleanolic acid.
abstract: Hydrogen sulfide-releasing oleanolic acid (HS-OA) is an emerging novel class of compounds and consists of an oleanolic acid (OA) and a H2S-releasing moiety. Although it exhibits improved anti-inflammatory activity, its potency in human cancers has not been understood yet. In this study, we examined the effects of HS-OA on the growth of liver cancer cell lines and the underlying mechanisms.HS-OA inhibited the growth of all four cancer cell lines studied, with potencies of 10- to 30-fold greater than that of its counterpart (OA). HS-OA induced significant apoptosis and decreased viability, clonogenic activity and migration of Hep G2 cells. Further studies showed that HS-OA resulted in the reduction of YAP expression and its downstream targets, CTGF and CYR 61, thus promoting cell apoptosis. In addition, HS-OA caused a decrease of 14-3-3γ expression, which led to Bad translocation to the mitochondria, ΔΨm loss, cytochrome c release, caspase activation and a recovery of 14-3-3γ reversed these effects induced by HS-OA.These findings indicate that YAP and 14-3-3γ are involved in HS-OA's effects on liver cancer cells and identifying HS-OA as a potential new drug candidate for cancer therapy.
authors.affiliation: College of Life Sciences, Nanjing Normal University, Nanjing, China.|Jiangsu Key Laboratory of 3D Printing Equipment and Manufacturing, Nanjing Normal University, Nanjing, China.|Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Science, Nanjing Normal University, Nanjing, China.
authors.forename: Guanglin
authors.initials: G
authors.lastname: Xu
authors.affiliation: College of Life Sciences, Nanjing Normal University, Nanjing, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: College of Life Sciences, Nanjing Normal University, Nanjing, China.
authors.forename: Fangfang
authors.initials: F
authors.lastname: Wu
authors.affiliation: College of Life Sciences, Nanjing Normal University, Nanjing, China.
authors.forename: Na
authors.initials: N
authors.lastname: Wang
authors.affiliation: College of Life Sciences, Nanjing Normal University, Nanjing, China.
authors.forename: Wenli
authors.initials: W
authors.lastname: Zhou
authors.affiliation: College of Life Sciences, Nanjing Normal University, Nanjing, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.affiliation: College of Life Sciences, Nanjing Normal University, Nanjing, China.
authors.forename: Wang
authors.initials: W
authors.lastname: Pan
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, Soochew University, Jiangsu, China.
authors.forename: Guizhen
authors.initials: G
authors.lastname: Ao
authors.affiliation: Jiangsu Key Laboratory of 3D Printing Equipment and Manufacturing, Nanjing Normal University, Nanjing, China.
authors.forename: Jiquan
authors.initials: J
authors.lastname: Yang
mesh_terms: D048948:14-3-3 Proteins / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D006862:Hydrogen Sulfide / Q000737:chemistry / Q000494:pharmacology*; D008113:Liver Neoplasms / Q000378:metabolism*; D009828:Oleanolic Acid / Q000737:chemistry / Q000494:pharmacology*; D010750:Phosphoproteins / Q000378:metabolism; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins
chemical_list: D048948:14-3-3 Proteins; D048868:Adaptor Proteins, Signal Transducing; D000970:Antineoplastic Agents; D010750:Phosphoproteins; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins; C088374:YAP1 protein, human; D009828:Oleanolic Acid; D006862:Hydrogen Sulfide
keywords: 14-3-3; COX-2; HCC; Hep G2; YAP