Effects of silymarin in protection against cisplatin-induced renal cell death and in cancer-killing effect of cisplatin

Abstract

Cisplatin-induced nephrotoxicity has been accepted as an important obstacle for efficient cisplatin-based chemotherapy. Silymarin, a mixture of flovonolignans extracted from seeds of milk thistle, has been shown to possess various potential pharmacological properties; however, whether or not this agent selectively protects renal cells form cisplatin-induced cell death with no interfering effect on cancer cells is not clear. Therefore, potential of silymarin in protection of cisplatin-induced renal cell death without compromising effect on anti-cancer activity of cisplatin was demonstrated in this study. The results indicated that cisplatin induced both apoptosis and necrosis in HK-2 cells and caused a decrease in cell viability ∼ 40% and 60% at the doses of 25 and 100 µM. Pretreatment with 50–200 µM of silymarin significantly protected against cisplatin-induced cell death in a dose-dependent manner. In contrast, pretreatment of silymarin caused no significant change on cisplatin-induced cell death in H460 cells but significantly potentiated cisplatin-induced apoptosis in G361 cells. Although, cisplatin induced renal, lung cancer and melanoma cell death through the induction of hydrogen peroxide (H2O2) and hydroxyl radical (˙OH), silymarin still selective protected only renal cell by its anti-oxidant activites against H2O2 and ˙OH without an interfering effect on cisplatin-induced cytotoxicity in human lung cancer H460 cells. In addition, silymarin showed enhancement of cisplatin-induced melanoma G361 cell death due to the direct anti-cancer activity of silymarin. These findings revealed 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.