Curcumin as chemosensitizer

This overview presents curcumin as a significant chemosensitizer in cancer chemotherapy. Although the review focuses on curcumin and its analogues on multidrug resistance (MDR) reversal, the relevance of curcumin as a nuclear factor (NF)-KB blocker and sensitizer of many chemoresistant cancer cell lines to chemotherapeutic agents will also be discussed. One of the major mechanisms of MDR is the enhanced ability of tumor cells to actively efflux drugs, leading to a decrease in cellular drug accumulation below toxic levels. Active drug efflux is mediated by several members of the ATP-binding cassette (ABC) superfamily of membrane transporters, which have now been subdivided into seven families designated A through G. Among these ABC families, the classical MDR is attributed to the elevated expression of ABCB1 (Pgp), ABCC1 (MRP1), and ABCG2 (MXR). The clinical importance of Pgp, MRP1, and MXR for MDR and cancer treatment has led to the investigation of the inhibiting properties of several compounds on these transporters. At present, due in part to the disappointing results associated with the many side effects of synthetic modulators that have been used in clinical trials, current research efforts are directed toward the identification of novel compounds, with attention to dietary natural products. The advantage is that they exhibit little or virtually no side effects and do not further increase the patient's medication burden.