Tumor Suppressor p53 Can Protect Normal Cells Against Dendrosomal Curcumin-Induced Apoptosis

Abstract

Curcumin is a natural substance with anti-cancerous properties without many disadvantages of currently-used anticancer drugs. Its toxicity is significantly higher in tumor cells compared with normal cells. We hypothesized the difference of p53 function between normal and tumor cells as one of the presumable causes of this phenomenon. We knocked down the expression of p53 in normal fibroblasts using anti-p53 siRNA and subsequently explored the effects caused by dendrosomal curcumin- a novel nanoformulation of curcumin- on these cells in terms of apoptosis induction and gene expression analysis. The results of MTT assay demonstrated dendrosomal curcumin is selectively cytotoxic for melanoma cancer cells without any considerable effects on normal fibroblasts. Knocking-down of p53 in normal fibroblast cells caused increase of NF-κB1 and decrease of p21 expression level. Treating p53-suppressed normal fibroblast cells with dendrosomal curcumin led to a robust increase in apoptosis rate of the cells. Taken together, these results imply the fact that p53 can protect normal cells from dendrosomal curcumin-induced apoptosis.Therefore, dendrosomal curcumin- in addition to being a chemotherapeutic compound-represents potential capacities to be used as an effective chemopreventive agent.