Journal
ONCOTARGET
Volume 7, Issue 32, Pages 52150-52165Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.10663
Keywords
YAP; 14-3-3; COX-2; HCC; Hep G
Categories
Funding
- Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)
- Scientific Research Foundation for the Returned Overseas Chinese Scholars, State Education Ministry (SRF for ROCS, SEM) [2015311]
- National Natural Science Foundation of China [61273243]
- Natural Science Foundation of Jiangsu Province [BM2013006]
- NSFC for Talents Training in Basic Science [J1103507, J1210025]
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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 G(2) 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 14-3-3 gamma expression, which led to Bad translocation to the mitochondria, Delta Psi m loss, cytochrome c release, caspase activation and a recovery of 14-3-3 gamma reversed these effects induced by HS-OA. These findings indicate that YAP and 14-3-3 gamma 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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