Curcumin enhances temsirolimus-induced apoptosis in human renal carcinoma cells through upregulation of YAP/p53.

Abstract

Curcumin has frequently been used as a therapeutic agent in the treatment of various types of disease and is known to enhance the drug sensitivity of cells. In the present study, the combined effect of curcumin and temsirolimus treatment on apoptosis in human renal cell carcinoma (RCC) cells was investigated. Temsirolimus is an inhibitor of the mechanistic target of rapamycin signaling pathway and used in the first-line treatment of metastatic RCC. It was demonstrated that curcumin combined with temsirolimus markedly induced apoptosis in RCC cells, however this effect was not observed following curcumin or temsirolimus treatment alone. Co-treatment with temsirolimus and curcumin led to the activation of cleaved poly ADP-ribose polymerase and caspase 3, upregulation of p53 expression and nuclear translocation, and downregulation of B-cell lymphoma 2 protein expression. Furthermore, curcumin treatment was demonstrated to increase Yes-associated protein (YAP) expression in a time-dependent manner, which was concurrent with the curcumin-induced expression pattern of p53 after 2 h. In addition, knockdown of YAP by small interfering RNA caused the attenuation of curcumin-induced increased p53 expression in RCC cells. In conclusion, the present results indicate that combined curcumin and temsirolimus treatment has a synergistic effect on apoptosis in human RCC cells, through the activation of p53. Mechanistically, YAP is essential in the induction of p53 expression by curcumin. Furthermore, the results suggest that pre-treatment or co-treatment of cells with low concentration curcumin enhances the response to targeted drugs, and this presents a potentially novel and efficient strategy to overcome drug resistance in human RCC.