The alpha-mangostin prevention on cisplatin-induced apoptotic death in LLC-PK1 cells is associated to an inhibition of ROS production and p53 induction

Abstract

Cisplatin (CDDP) is a widely useful chemotherapeutic agent for the treatment of tumors including lung, ovary and testis. Acute renal injury, however, is the main side effect observed after CDDP treatment. This side effect is related to the apoptotic death in proximal tubular cells in the kidney and p53 protein has a central role in this process. On the other hand, alpha-mangostin (alpha-M), a xanthone derived from the pericarp of mangosteen, exerts a renoprotective effect against cisplatin-induced renal damage in rats. The aim of this study was to evaluate whether alpha-M protects proximal tubule renal epithelial cells (LLC-PK1) from CDDP-induced apoptotic death. Cells were co-incubated with 5 microM alpha-M and 100 microM CDDP for 24h. It was found that alpha-M attenuated the following alterations: the apoptotic cell death, the increase in reactive oxygen species (ROS), the glutathione depletion and the increase in p53 expression induced by CDDP. In conclusion, the preventive effect of alpha-M on CDDP-induced apoptotic death is associated to the inhibition of p53 expression and ROS generation.