Pure curcumin inhibits exogenous Wilms' tumor (WT1) (+/+) isoform protein via degradation pathway and protein kinase C in transfected U937 cells

Wilms' tumor (WT1) gene overexpresses in leukemic cells which is alternatively spliced at two sites, yielding four isoforms: WT1 (+/+), (+/-), (-/+), and (-/-). Curcumin is one of major active components of the spice turmeric, widely known as anticancer. This study investigated the effects and inhibitory mechanism of pure curcumin on WT1 isoform-transfected U937 cells. WT1 transfected U937 cells were initially treated for 24 h, with 10 μM pure curcumin. Pure curcumin exhibited a strong inhibitory effect on WT1 (+/+) mRNA level detected by real time PCR. Treatment of WT1 transfected U937 cells with non-cytotoxic doses (10, 15, and 17 μM) of pure curcumin decreased WT1 protein levels in a dose dependent manner. Pure curcumin at the concentration of 15 μM significantly decreased the protein levels of the WT (+/+) isoform in a time-dependent manner. It also decreased exogenous WT1 (+/+) protein half-life. WT1 protein expression was inhibited by protein kinase C inhibitor (GF109203x) suggesting that pure curcumin decreased exogenous WT1 (+/+) expression in transfected U937 cells via protein kinase C during post-translational processing.