Curcumin Induces Apoptosis and Inhibits Metalloproteinase Activity in Renal Cancer Cell Line

Kim, Dae Gon; Kwon, Taeg Kyu; Park, Jong Wook; Lee, Kyung Seop

Abstract

PURPOSE
Curcumin is the major constitute of turmeric powder extracted from the rhizomes of the plant Curcuma longa. We investigated that the effect of curcumin on regulatory protein of cell cycle, induction of apoptosis and metalloproteinase (MMP) activity in Caki cells, renal cell carcinoma (RCC) line.
MATERIALS AND METHODS
The Caki cells were treated with curcumin for 24 h and cells were visually monitored and photographed. The cell viability was determined by trypan blue exclusion staining. The expression levels of cell cycle regulatory proteins and apoptosis regulatory proteins were determined by Western blot. To address the significance of caspase activation in curcumin-induced apoptosis, we used a general and potent inhibitor of caspases, z-VAD-fmk. The expression and secretion of MMP were determined by gelatin zymography.
RESULTS
Treatment with curcumin produced morphological changing and DNA fragmentation in Caki cells. It also inhibited cellular growth and reduced cell viability in Caki cells. Inhibition of cell growth was associated with down-regulation of cell cycle regulatory proteins. Reduction of cell viability was associated with caspase 3 activation. The elevated caspase 3 activity in curcumin treated Caki cells are correlated with down-regulation of XIAP and cIAP1. Caspase inhibitor co-treated cells abolished curcumin-induced caspase 3 activity. The release of cytochrome c in curcumin-induced Caki cells was dose-dependent manners. Although MMP-2 expression levels were not significantly altered, however, the expression and secretion levels of MMP-9 were induced by PMA dose-dependent manners.
CONCLUSIONS
Curcumin induces apoptosis and inhibit invasion by down regulation of regulatory protein of cell cycle, apoptosis related protein and MMP activity. These findings have implications for developing curcumin-based anticancer prevention or therapy of RCC.