Curcumin: A Potent Modulator of Multiple Enzymes in Multiple Cancers.

Curcumin (diferuloylmethane) is the biphenolic active compound of turmeric. Curcumin has been used for hundreds of years to treat various ailments. Curcumin has been reported to exert numerous pharmacological effects by modulating multiple molecular targets including those involved in the pathogenesis of cancer. Cancer has been characterized as the dysregulation of cell signaling pathways through gradual alteration of regulatory proteins and through gene mutation. Curcumin is a highly pleiotropic molecule that modulates several intracellular signaling pathways in cancer. The pleiotropic activities of curcumin have been attributed to its novel molecular structure. Based on its β-diketone moiety, curcumin exists in keto-enol tautomers, and this tautomerism favors interaction and binding with a wide range of enzymes. Several studies have shown modulation of numerous signaling enzymes by curcumin including, LOX, COX-2, XO, proteasomes, Ca(2+)-ATPase of sarcoplasmic reticulum, MMPs, HAT, HDAC, DNMT1, DNA polymerase λ, ribonucleases, GloI, protein kinases (PKA, PKB, PKC, v-Src, GSK-3β, ErbB2), protein reductases (TrxR1, AR), GSH, ICDHs, peroxidases (Prx1, Prx2, Prx6) by treatment with curcumin. Various biophysical analyses have been reported, which shows the underlying molecular interaction of curcumin with multiple targets in terms of binding affinities. The current chapter describes how curcumin binds and modulates multiple enzymes involved cancer. Published clinical trial studies with curcumin in cancer management will also be discussed.