4.6 Article

Ginsenoside 20(S)-protopanaxadiol induces cell death in human endometrial cancer cells via apoptosis

期刊

JOURNAL OF GINSENG RESEARCH
卷 45, 期 1, 页码 126-133

出版社

KOREAN SOC GINSENG
DOI: 10.1016/j.jgr.2020.02.002

关键词

endometrial cancer; 20(S)-PPD; apoptosis; xenograft; athymic mice

资金

  1. KRF grant - Korean Government (MEST) [2012R1A1B3000486]
  2. Ajou University
  3. National Research Foundation of Korea (NRF) - Korean government (MSIT) [2019005607]
  4. KBRI basic research program through Korea Brain Research Institute - Ministry of Science and ICT [19-BR-03-02]
  5. National Research Foundation of Korea [21-BR-03, 2012R1A1B3000486] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)

向作者/读者索取更多资源

20(S)-protopanaxadiol (20(S)-PPD) inhibits human endometrial cancer cell proliferation by inducing cell death via a caspase-mediated apoptosis pathway, and it also shows tumor growth inhibition in xenograft mouse models.
Background: 20(S)-protopanaxadiol (20(S)-PPD), one of the aglycone derivatives of major ginsenosides, has been shown to have an anticancer activity toward a variety of cancers. This study was initiated with an attempt to evaluate its anti-cancer activity toward human endometrial cancer by cell and xenograft mouse models. Methods: Human endometrial cancer (HEC)- 1A cells were incubated with different 20( S)-PPD concentrations. 20(S)-PPD cytotoxicity was evaluated using MTT assay. Apoptosis was detected using the annexin V binding assay and cell cycle analysis. Cleaved poly (ADP-ribose) polymerase (PARP) and activated caspase-9 were assessed using western blotting. HEC-1A cell tumor xenografts in athymic mice were generated by inoculating HEC-1A cells into the flank of BALB/c female mice and explored to validate 20(S)-PPD anti-endometrial cancer toxicity. Results: 20(S)-PPD inhibited HEC-1A cell proliferation in a dose-dependent manner with an IC50 value of 3.5 mM at 24 h. HEC-1A cells morphologically changed after 20(S)-PPD treatment, bearing resemblance to Taxol-treated cells. Annexin V-positive cell percentages were 0%, 10.8%, and 58.1% in HEC-1A cells when treated with 0, 2.5, and 5 mM of 20(S)-PPD, respectively, for 24 h. 20(S)-PPD subcutaneously injected into the HEC-1A cell xenograft-bearing mice three times a week for 17 days manifested tumor growth inhibition by as much as 18% at a dose of 80 mg/kg, which sharply contrasted to controls that showed an approximately 2.4-fold tumor volume increase. These events paralleled caspase-9 activation and PARP cleavage. Conclusion: 20(S)-PPD inhibits endometrial cancer cell proliferation by inducing cell death via a caspasemediated apoptosis pathway. Therefore, the 20(S)-PPD-like ginsenosides are endowed with ample structural information that could be utilized to develop other ginsenoside-based anticancer agents. (C) 2020 The Korean Society of Ginseng. Publishing services by Elsevier B.V.

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