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  3. Gypenoside L Inhibits Proliferation of Liver and Esophageal Cancer Cells by Inducing Senescence

Gypenoside L Inhibits Proliferation of Liver and Esophageal Cancer Cells by Inducing Senescence

  • Molecules. 2019 Mar 18;24(6):1054. doi: 10.3390/molecules24061054.
Jingxin Ma 1,  Xiaopeng Hu 2,  Chenghui Liao 3,  Haitao Xiao 4,  Qinchang Zhu 5,  Ying Li 6,  Zhigang Liu 7,  Anjin Tao 8,  Zhendan He 9 10,  Chenshu Xu 11,  Kai Zheng 12
Affiliations

Affiliations

  • 1 School of Pharmaceutical Sciences, Shenzhen Key Laboratory of Novel Natural Health Care Products, Engineering Laboratory of Shenzhen Natural small molecule Innovative Drugs, Health Science Center, Shenzhen University, Shenzhen 518060, China. 18565811720@163.com.
  • 2 School of Pharmaceutical Sciences, Shenzhen Key Laboratory of Novel Natural Health Care Products, Engineering Laboratory of Shenzhen Natural small molecule Innovative Drugs, Health Science Center, Shenzhen University, Shenzhen 518060, China. hu54398@2008.sina.com.
  • 3 School of Pharmaceutical Sciences, Shenzhen Key Laboratory of Novel Natural Health Care Products, Engineering Laboratory of Shenzhen Natural small molecule Innovative Drugs, Health Science Center, Shenzhen University, Shenzhen 518060, China. liao.chenghui66@gmail.com.
  • 4 School of Pharmaceutical Sciences, Shenzhen Key Laboratory of Novel Natural Health Care Products, Engineering Laboratory of Shenzhen Natural small molecule Innovative Drugs, Health Science Center, Shenzhen University, Shenzhen 518060, China. Xhaitao@szu.edu.cn.
  • 5 School of Pharmaceutical Sciences, Shenzhen Key Laboratory of Novel Natural Health Care Products, Engineering Laboratory of Shenzhen Natural small molecule Innovative Drugs, Health Science Center, Shenzhen University, Shenzhen 518060, China. Zhuqc@szu.edu.cn.
  • 6 School of Pharmaceutical Sciences, Shenzhen Key Laboratory of Novel Natural Health Care Products, Engineering Laboratory of Shenzhen Natural small molecule Innovative Drugs, Health Science Center, Shenzhen University, Shenzhen 518060, China. li.ying@szu.edu.cn.
  • 7 School of Pharmaceutical Sciences, Shenzhen Key Laboratory of Novel Natural Health Care Products, Engineering Laboratory of Shenzhen Natural small molecule Innovative Drugs, Health Science Center, Shenzhen University, Shenzhen 518060, China. lzg@szu.edu.cn.
  • 8 Hybio Pharmaceutical Co., Ltd. Shenzhen 518057, China. taoanjin@hybio.com.cn.
  • 9 School of Pharmaceutical Sciences, Shenzhen Key Laboratory of Novel Natural Health Care Products, Engineering Laboratory of Shenzhen Natural small molecule Innovative Drugs, Health Science Center, Shenzhen University, Shenzhen 518060, China. hezhendan@szu.edu.cn.
  • 10 Guangdong Key Laboratory for Genome Stability & Human Disease Prevention, Health Science Center, Shenzhen University, Shenzhen 518060, China. hezhendan@szu.edu.cn.
  • 11 School of Pharmaceutical Sciences, Shenzhen Key Laboratory of Novel Natural Health Care Products, Engineering Laboratory of Shenzhen Natural small molecule Innovative Drugs, Health Science Center, Shenzhen University, Shenzhen 518060, China. cshuxu@szu.edu.cn.
  • 12 School of Pharmaceutical Sciences, Shenzhen Key Laboratory of Novel Natural Health Care Products, Engineering Laboratory of Shenzhen Natural small molecule Innovative Drugs, Health Science Center, Shenzhen University, Shenzhen 518060, China. zhengk@szu.edu.cn.
PMID: 30889805 DOI: 10.3390/molecules24061054
Abstract

Senescence is an irreversible state of cell cycle arrest that can be triggered by multiple stimuli, such as oxygen reactive species and DNA damage. Growing evidence has proven that senescence is a tumor-suppressive approach in Cancer treatment. Therefore, developing novel agents that modulate senescence may be an alternative strategy against Cancer. In our study, we investigated the inhibitory effect of gypenoside L (Gyp-L), a saponin isolated from Gynostemma pentaphyllum, on Cancer cell growth. We found that Gyp-L increased the SA-β-galactosidase activity, promoted the production of senescence-associated secretory cytokines, and inhibited cell proliferation of human liver and esophageal Cancer cells. Moreover, Gyp-L caused cell cycle arrest at S phase, and activated senescence-related cell cycle inhibitor proteins (p21 and p27) and their upstream regulators. In addition, Gyp-L activated p38 and ERK MAPK pathways and NF-κB pathway to induce senescence. Consistently, adding chemical inhibitors efficiently counteracted the Gyp-L-mediated senescence, growth inhibition, and cell cycle arrest in Cancer cells. Furthermore, treatment with Gyp-L, enhanced the cytotoxicity of clinic therapeutic drugs, including 5-fluorouracil and cisplatin, on Cancer cells. Overall, these results indicate that Gyp-L inhibits proliferation of Cancer cells by inducing senescence and renders Cancer cells more sensitive to chemotherapy.

Keywords

MAPK; NF-κB signaling; cell cycle arrest; chemoresistance; gypenoside L; senescence.

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