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

Hantae Jo, Dongmin Jang, Sun Kyu Park, Mi Gi Lee, Byungsun Cha, Chaewon Park, Yong Sub Shin, Hyein Park, Jin myoung Baek, Hyojin Heo, Sofia Brito, Hyun Gyu Hwan, Sehyun Chae, Shao wei Yan, Changho Lee, Churl K. Min, Bum Ho Bin

Research output: Contribution to journalArticlepeer-review

Abstract

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 μM 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 μM 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 caspase-mediated 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.

Original languageEnglish
Pages (from-to)126-133
Number of pages8
JournalJournal of Ginseng Research
Volume45
Issue number1
DOIs
StatePublished - 2021 Jan

Keywords

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

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