Currently available breast cancer preventives only reduce the incidence of hormonally driven neoplasms. Curcumin, an isolate of the spice turmeric, has been shown to downregulate the Wnt and Notch signaling pathways which regulate stem cell fate. Piperine, an alkaloid isolate of black pepper, enhances systemic bioavailability of curcumin in rats and humans by enhancing absorption, decreasing CYP3A4 and conjugation and blockading P-glycoprotein. We compared the effectiveness of 98% pure curcumin alone, piperine alone, to curcumin + piperine in decreasing human breast stem cell self renewal (mammosphere formation in suspension culture) and differentiation on collagen with serum based media. Curcumin alone decreased mammosphere formation by 50% at 10 μM concentration. At and above 25 μM concentration curcumin for 4 hrs of exposure, all cells died and no mammospheres were formed. With the addition of 10 μM piperine, curcumin 5 μM was sufficient to produce a 50% decrease in mammosphere number and no mammospheres formed due to universal cell death at 10μM curcumin and above. Piperine alone had no effect on mammopshere formation. Using in situ staining for CK 14 and CK 10, differentiated myoepithelial and luminal colonies formed in the presence of both curcumin and curcumin plus piperine. The number of differentiated colonies in clonogenic density on collagen dropped by 50% when 5 μM curcumin + 10 μM piperine was present from the time of plating. If cells were plated for 48 hrs before curcumin and piperine were added, there was no difference in colony number. Both myoepithelial and luminal cells formed from breast stem cells. Piperine alone had no effect on differentiated colony formation. These data suggest that curcumin may decrease risk of breast cancer by reducing breast stem cell self renewal and enhancing differentiation of breast stem cells. Piperine enhances breast stem cell sensitivity to curcumin.

99th AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA