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
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Guanglin Xu1,2,3, Jing Wang1, Fangfang Wu1, Na Wang1, Wenli Zhou1, Qian Wang1, Wang Pan1, Guizhen Ao4, Jiquan Yang2
1College of Life Sciences, Nanjing Normal University, Nanjing, China
2Jiangsu Key Laboratory of 3D Printing Equipment and Manufacturing, Nanjing Normal University, Nanjing, China
3Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Science, Nanjing Normal University, Nanjing, China
4Department of Medicinal Chemistry, School of Pharmacy, Soochew University, Jiangsu, China
Jiquan Yang, email: [email protected]
Keywords: YAP, 14-3-3, COX-2, HCC, Hep G2
Received: March 31, 2016 Accepted: June 30, 2016 Published: July 18, 2016
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.
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