LNCaP公司
细胞毒性
程序性细胞死亡
蛋白激酶B
细胞生物学
细胞凋亡
细胞生长
细胞
化学
癌细胞
癌症研究
生物
信号转导
生物化学
癌症
体外
遗传学
作者
Kotamballi N. Chidambara Murthy,G.K. Jayaprakasha
出处
期刊:Toxicology
[Elsevier]
日期:2015-03-01
卷期号:329: 88-97
被引量:25
标识
DOI:10.1016/j.tox.2015.01.008
摘要
Obacunone and obacunone glucoside (OG) are naturally occurring triterpenoids commonly found in citrus and other plants of the Rutaceae family. The current study reports the mechanism of cytotoxicity of citrus-derived obacunone and OG on human androgen-dependent prostate cancer LNCaP cells. Both limonoids exhibited time- and dose-dependent inhibition of cell proliferation, with more than 60% inhibition of cell viability at 100 μM, after 24 and 48 h. Analysis of fragmentation of DNA, activity of caspase-3, and cytosolic cytochrome-c in the cells treated with limonoids provided evidence for activation of programmed cell death by limonoids. Treatment of LNCaP cells with obacunone and OG resulted in dose-dependent changes in expression of proteins responsible for the induction of programmed cell death through the intrinsic pathway and down-regulation of Akt, a key molecule in cell signaling pathways. In addition, obacunone and OG also negatively regulated an inflammation-associated transcription factor, androgen receptor, and prostate-specific antigen, and activated proteins related to the cell cycle, confirming the ability of limonoids to induce cytotoxicity through multiple pathways. The results of this study provided, for the first time, an evidence of the cytotoxicity of obacunone and OG in androgen-dependent human prostate cancer cells.
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