Oleanolic acid isolated from ethanolic extract of Phytolacca decandra induces apoptosis in A375 skin melanoma cells: drug-DNA interaction and signaling cascade

查看全文 作　　者：Samrat [1]Ghosh;Kausik [1]Bishayee;Anisur Rahman Khuda-[1]Bukhsh

机构地区：[1]Cytogenetics and Molecular Biology Laboratory,Department of Zoology,University of Kalyani

出　　处：《Journal of Integrative Medicine》索引2014年第12卷第2期,共13页

基　　金：the Boiron Laboratories,Lyon,France for partial financial support of the work 摘　　要：OBJECTIVE: Oleanolic acid(OA) has been reported to have anticancer effects, but the extent of its cytotoxicity, its ability to interact with nuclear DNA, its action against skin melanoma, as well as the molecular mechanism of its action against cell proliferation and in support of cell death are still unexplored. This led us to examine the efficacy of OA, a bioactive compound isolated from Phytolacca decandra, on these issues in the present investigation.METHODS: Studies related to analyses of cell viability, drug-DNA interaction, cell proliferation, cell cycle and epidermal growth factor receptor(EGFR) activity were performed. To investigate whether cells undergo apoptosis, studies like fl uorescence microscopy, poly(ADP-ribose) polymerase(PARP) degradation, annexin V-fl uorescein isothiocyanate/propidium iodide assay, alteration in mitochondrial membrane potential and activity of some relevant signaling proteins were performed.RESULTS: OA displayed a minimal and negligible cytotoxic effect on normal HaCaT cells(skin keratinocytes) and peripheral blood mononuclear cells but by contrast it reduced A375 cell viability significantly. OA interacted with nuclear DNA quickly after exposure. It acted as an antiproliferative agent. It suppressed EGFR activity. OA administration led the cells to mitochondriadependent caspase 3-mediated apoptosis.CONCLUSION: OA interacts with cellular DNA, inhibits proliferation possibly through modulating EGFR activity and induces mitochondria-dependent caspase 3-mediated apoptosis in A375 cells which would qualify it as a potent anticancer agent. 关键词：黑色素细胞相互作用细胞凋亡抗癌药物齐墩果酸信号传导乙醇提取物皮肤

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Oleanolic acid isolated from ethanolic extract of Phytolacca decandra induces apoptosis in A375 skin melanoma cells: drug-DNA interaction and signaling cascade

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