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

• Published in: Journal of ginseng research Vol. 45; no. 1; pp. 126 - 133
• Main Authors: Jo, Hantae, Jang, Dongmin, Park, Sun Kyu, Lee, Mi-Gi, Cha, Byungsun, Park, Chaewon, Shin, Yong Sub, Park, Hyein, Baek, Jin-myoung, Heo, Hyojin, Brito, Sofia, Hwan, Hyun Gyu, Chae, Sehyun, Yan, Shao-wei, Lee, Changho, Min, Churl K., Bin, Bum-Ho
• Format: Journal Article
• Language: English
• Published: Korea (South) Elsevier B.V 01.01.2021; 고려인삼학회; Elsevier
• Subjects: 20(S)-PPD; animal disease models; antineoplastic activity; apoptosis; athymic mice; caspase-9; cell proliferation; cytotoxicity; endometrial cancer; females; ginsenosides; inhibitory concentration 50; mice; NAD ADP-ribosyltransferase; neoplasm cells; sapogenins; uterine neoplasms; xenograft; 기타의약학; endometrial cancer; athymic mice; apoptosis; xenograft; 20(S)-PPD
• ISSN: 1226-8453; 2093-4947
• DOI: 10.1016/j.jgr.2020.02.002

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. 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. 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. 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.