Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand.
Pharm Biol. 2011 Oct;49(10):1082-90. doi: 10.3109/13880209.2011.568506. Epub 2011 May 18.
Cisplatin-induced nephrotoxicity has been accepted as an important obstacle for efficient cisplatin-based chemotherapy. Silymarin from seeds of milk thistle [Silybum marianum L. (Asteraceae)] has been shown to possess various potential pharmacological properties; however, whether or not this agent selectively protects renal cells from cisplatin-induced cell death with no interfering effect on cancer cells is not clear.
Potential of silymarin in protection of cisplatin-induced renal cell death without compromising effect on anticancer activity of cisplatin was demonstrated in this study.
Cisplatin-induced cell death was evaluated in human proximal tubular HK-2, lung carcinoma H460, and melanoma G361 cells using MTT, Hoechst 33342, and propidium iodide assays.
Cisplatin induced both apoptosis and necrosis in HK-2 cells and caused a decrease in cell viability by ~40% and 60% at the doses of 25 and 100 µM, respectively. Pretreatment with 25-200 µM of silymarin significantly protected against cisplatin-induced cell death in a dose-dependent manner. In contrast, pretreatment of silymarin (25-100 µM) caused no significant change on cisplatin-induced cell death in H460 cells but significantly potentiated cisplatin-induced apoptosis in G361 cells.
These findings reveal the selectivity of silymarin in protection of renal cells from cisplatin-induced cell death and could be beneficial for the development of this considerately safe compound as a renoprotective agent.
顺铂诱导的肾毒性已被认为是高效顺铂化疗的一个重要障碍。水飞蓟素(奶蓟草的种子)已被证明具有多种潜在的药理作用;然而,这种药物是否能选择性地保护肾细胞免受顺铂诱导的细胞死亡,而对癌细胞没有干扰作用尚不清楚。
本研究旨在证明水飞蓟素在保护顺铂诱导的肾细胞死亡而不影响顺铂抗癌活性方面的潜力。
采用 MTT、Hoechst 33342 和碘化丙啶法评估顺铂诱导的人近端肾小管 HK-2、肺癌 H460 和黑素瘤 G361 细胞死亡。
顺铂诱导 HK-2 细胞凋亡和坏死,并使细胞活力分别在 25 和 100 μM 剂量下下降约 40%和 60%。25-200 μM 水飞蓟素预处理可显著地、剂量依赖性地保护顺铂诱导的细胞死亡。相反,水飞蓟素(25-100 μM)预处理对 H460 细胞中顺铂诱导的细胞死亡没有显著影响,但显著增强了 G361 细胞中顺铂诱导的细胞凋亡。
这些发现揭示了水飞蓟素在保护肾细胞免受顺铂诱导的细胞死亡方面的选择性,这可能有助于开发这种被认为是安全的化合物作为肾保护剂。