Journal
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
Volume 64, Issue 40, Pages 7520-7529Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.jafc.6b03519
Keywords
ginsenoside Rh2; octyl ester derivative; cell cycle; HepG2 cells; Akt; MAPKs
Funding
- National Natural Science Foundation of China [31360370]
- Foundation of Jiangxi Educational Committee [GJJ14092]
- research Foundation for Young Scientists of State Key Laboratory of Food Science and Technology, Nanchang University, China [SKLF-QN-201515]
- Research Program of State Key Laboratory of Food Science and Technology, Nanchang University [SKLF-ZZA- 201303]
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Ginsenoside Rh2 is a potential active metabolite of ginseng that has antitumor activity against a variety of tumor cells. Previously, we reported that Rh2-O, an octyl ester derivative of ginsenoside Rh2, had a higher anticancer activity than Rh2 through activating the intrinsic apoptotic pathway. In this study, we found that the extrinsic apoptotic pathway was also involved in Rh2-O-induced HepG2 cells apoptosis as evidenced by the up-regulation of Fas, FasL, TNFR1, and TNF-alpha as well as the cleavage of caspase 8. Moreover, flow cytometric analysis demonstrated that Rh2-O induced G1 cell cycle arrest in HepG2 cells. Rh2-O-induced G1 phase arrest was accompanied by the down-regulation of cyclin D3 and cyclin E and cyclin-dependent kinases (CDK) 4 and 6 and the up-regulation of p21(WAF1/CIP1) and p27(KIP1). In addition, Rh2-O down-regulated the phosphorylation of Akt, and its inhibitor LY294002 promoted Rh2-O-induced G1 phase arrest. Rh2-O treatment also activated p38 MAPK, JNK, and ERK expression. Inhibitors of p38 MAPK (SB203580), but not those of JNK (SP600125) or ERK (PB98095), promoted Rh2-O-induced G1 phase arrest in HepG2 cells. These results indicated that the disruption of Akt and p38 MAPK cascades played a pivotal role in Rh2-O-induced G1 phase arrest.
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