12-Chloracetyl-PPD, a novel dammarane derivative, shows anti-cancer activity via delay the progression of cell cycle G2/M phase and reactive oxygen species-mediate cell apoptosis
| Autor: | Yuan Yuan Sun, Chen Zhao, Fan Zhi Qu, Xu De Wang, Yu Qing Zhao |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Cell cycle checkpoint Cell Panax Apoptosis Biology 03 medical and health sciences 0302 clinical medicine Cell Line Tumor medicine Humans Cell Proliferation Pharmacology chemistry.chemical_classification Reactive oxygen species Cancer Cell cycle medicine.disease Antineoplastic Agents Phytogenic Triterpenes G2 Phase Cell Cycle Checkpoints 030104 developmental biology medicine.anatomical_structure chemistry Cell culture 030220 oncology & carcinogenesis Cancer cell Immunology Cancer research M Phase Cell Cycle Checkpoints Reactive Oxygen Species |
| Zdroj: | European journal of pharmacology. 798 |
| ISSN: | 1879-0712 |
| Popis: | (20R)-Dammarane-3β, 12β, 20, 25-tetrol (25-OH-PPD) is a ginsenoside isolated from Panax ginseng (C. A. Meyer). This compound exhibits anti-cancer activities on many human cancer cell lines. In this study, we investigated anti-cancer mechanisms of 12β-O-(L-Chloracetyl)-dammar-20(22)-ene-3β,25-diol(12-Chloracetyl-PPD), a modified 25-OH-PPD. We found that compound 12-Chloracetyl-PPD resulted in a concentration-dependent inhibition of viability in prostate, breast, and gastric cancer cells, without affecting the viability of normal cell (human gastric epithelial cell line-GES-1, hair follicle dermal papilla cell line-HHDPC and rat myocardial cell line-H9C2). In MDA-MB-435 and C4-2B cancer cells, 12-Chloracetyl-PPD induced G2/M cell cycle arrest, down-regulated mouse double minute 2 (MDM2) expression, up-regulated p53 expression, triggered apoptosis, and stimulated reactive oxygen species production. Apoptosis can be attenuated by the reactive oxygen species scavenger N-acetylcysteine. Our results suggested that compound 12-Chloracetyl-PPD showed obvious anti-cancer activity based on delaying cell cycle arrest and inducing cell apoptosis by reactive oxygen species production, which supported development of 12-Chloracetyl-PPD as a potential agent for cancer chemotherapy. |
| Databáze: | OpenAIRE |
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