Drug Design, Development and Therapy (Aug 2015)

20(S)-ginsenoside Rg3 promotes senescence and apoptosis in gallbladder cancer cells via the p53 pathway

  • Zhang F,
  • Li M,
  • Wu X,
  • Hu Y,
  • Cao Y,
  • Wang X,
  • Xiang S,
  • Li H,
  • Jiang L,
  • Tan Z,
  • Lu W,
  • Weng H,
  • Shu Y,
  • Gong W,
  • Wang X,
  • Zhang Y,
  • Shi W,
  • Dong P,
  • Gu J,
  • Liu Y

Journal volume & issue
Vol. 2015, no. default
pp. 3969 – 3987

Abstract

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Fei Zhang,* Maolan Li,* Xiangsong Wu,* Yunping Hu, Yang Cao, Xu’an Wang, Shanshan Xiang, Huaifeng Li, Lin Jiang, Zhujun Tan, Wei Lu, Hao Weng, Yijun Shu, Wei Gong, Xuefeng Wang, Yong Zhang, Weibin Shi, Ping Dong,# Jun Gu,# Yingbin Liu#Department of General Surgery and Laboratory of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, Institute of Biliary Tract Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China *These authors contributed equally to this work #These authors jointly directed this work Abstract: Gallbladder cancer (GBC), the most frequent malignancy of the biliary tract, is associated with high mortality and extremely poor prognosis. 20(S)-ginsenoside Rg3 (20(S)-Rg3) is a steroidal saponin with high pharmacological activity. However, the anticancer effect of 20(S)-Rg3 in human GBC has not yet been determined. In this study, we primarily found that 20(S)-Rg3 exposure suppressed the survival of both NOZ and GBC-SD cell lines in a concentration-dependent manner. Moreover, induction of cellular senescence and G0/G1 arrest by 20(S)-Rg3 were accompanied by a large accumulation of p53 and p21 as a result of murine double minute 2 (MDM2) inhibition. 20(S)-Rg3 also caused a remarkable increase in apoptosis via the activation of the mitochondrial-mediated intrinsic caspase pathway. Furthermore, intraperitoneal injection of 20(S)-Rg3 (20 or 40 mg/kg) for 3 weeks markedly inhibited the growth of xenografts in nude mice. Our results demonstrated that 20(S)-Rg3 potently inhibited growth and survival of GBC cells both in vitro and in vivo. 20(S)-Rg3 attenuated GBC growth probably via activation of the p53 pathway, and subsequent induction of cellular senescence and mitochondrial-dependent apoptosis. Therefore, 20(S)-Rg3 may be a potential chemotherapeutic agent for GBC therapy.Keywords: gallbladder cancer, 20(S)-ginsenoside Rg3, senescence, apoptosis, p53 pathway