Curcumin Cell Signaling: A Possible Target for Chemotherapy

Many components that are derived from medicinal or dietary plants, known as phytochemicals, posses chemopreventive properties. Curcumin, the active chemical of the spice turmeric, exhibits anticancer activity in several cancer cell lines. Nuclear factor kappa B (NF-êB) and activator protein-1 (AP-1) play a critical role in the transcriptional regulation of genes that have been shown to suppress apoptosis and induce cellular transformation, proliferation, invasion, metastasis, chemo-resistance, radioresistance and inflammation. A number of studies have shown that curcumin exerts its anti-cancer effects through the suppression of activation of NF-êB and AP-1, and lead to the down-regulation of its target gene products COX-2, cyclin D1, Bcl-2, Bcl-xL, cIAP1, xIAP and survivin. On the other hand, Curcumin also is shown to induce cancer cell growth arrest and apoptosis in several cell models. Curcumin treatment up-regulates the expression of proteins involved in apoptosis and exhibits common apoptotic features like altered expression of Bcl-2 family of proteins, imbalanced mitochondrial trans-membrane permeability (ÄØm), release of cytochrome c, Smac, and AIF from mitochondria. These effects induce apoptosis via caspase-dependent and independent pathways. There are conflicting reports as to the role of curcumin in redox balance. It has been shown to act as potent scavenger of reactive oxygen species (ROS), and at the same time it induces free radical generation and significant cell death through apoptosis in other cancer cell models. Both in vivo and in vitro studies have shown that curcumin inhibit some of the enzyme activities which have important role in cell regulation. Curcumin acts as a potent inhibitor of Phosphorylase kinase (PhK), and Phospholipase D (PLD) under in vitro conditions. In vivo studies have shown that curcumin inhibits LPS induced expression of inducible nitric oxide synthase (iNOS), and also acts as a novel inhibitor of class I histone deacetylase (class I HDACs) such as HDAC1, HDAC3, and HDAC8. Apart from these, it has been shown that curcumin induces apoptosis of cancer cells through the generation of the sphingolipid metabolite ceramide. This review attempts to summarize curcumin cell signaling pathways responsible for cell growth arrest or apoptosis.