Ginsenoside 20(S)-protopanaxadiol induces cell death in human endometrial cancer cells via apoptosis
Autor: | Hyein Park, Sehyun Chae, Chaewon Park, Jin myoung Baek, Shao wei Yan, Mi Gi Lee, Yong Sub Shin, Bum-Ho Bin, Hyojin Heo, Changho Lee, Sun Kyu Park, Byungsun Cha, Sofia Brito, Dongmin Jang, Hantae Jo, Hyun Gyu Hwan, Churl K. Min |
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Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
Programmed cell death Cell Biochemistry Genetics and Molecular Biology (miscellaneous) 03 medical and health sciences chemistry.chemical_compound 20(S)-PPD 0302 clinical medicine Annexin lcsh:Botany medicine MTT assay xenograft Cytotoxicity athymic mice Cell growth apoptosis Molecular biology lcsh:QK1-989 030104 developmental biology medicine.anatomical_structure Complementary and alternative medicine chemistry Apoptosis 030220 oncology & carcinogenesis endometrial cancer Protopanaxadiol Research Article Biotechnology |
Zdroj: | Journal of Ginseng Research Journal of Ginseng Research, Vol 45, Iss 1, Pp 126-133 (2021) |
ISSN: | 1226-8453 |
Popis: | 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. |
Databáze: | OpenAIRE |
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