Present study shows that drug resistant human breast cancer cells are enriched in cancer stem-like cells (CSCs) and express elevated levels of Stat-3 signaling mediators, which contribute to CSC enrichment. Simvastatin (SVA) and gamma-tocotrienol (gammaT3) eliminate enriched CSCs and suppress expression of Stat-3 signaling mediators via inhibition of the mevalonate pathway and activation of de novo ceramide synthesis pathway, respectively. Combination of SVA+gammaT3 at low doses enhanced these actions via inhibition of the mevalonate pathway. Data demonstrate that SVA and gammaT3 alone or in combination possess the ability to eliminate CSCs in drug resistant human breast cancer cells.
