Curcumin Cell Signaling: A Possible Target for Chemotherapy

Order of Publishing in Issue: 
1
Volume :2
Issue :2
March, 2008
Page No: 
6-18
Authors: 
Shahanas Chathoth, Faisal Thayyullathil and Sehamuddin Galadari*
Address: 
Cell Signaling Laboratory, Department of Biochemistry, Faculty of Medicine and Health Sciences, UAE University P.O. Box 17666, Al Ain, UAE
Email-ID: 
sehamuddin@uaeu.ac.ae

Many components that are derived from medicinal or dietary plants, known as phytochemicals, posses chemopreventiveproperties. 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 inducecancer cell growth arrest and apoptosis in several  cell models. Curcumin treatment up-regulates theexpression of proteins involved in apoptosis and exhibits common apoptotic features like alteredexpression 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 inother cancer cell models. Both in vivo and in vitro studies have shown that curcumin inhibit some of the enzyme activities which have importantrole 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 IHDACs) 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 pathwaysresponsible for cell growth arrest or apoptosis.

Keywords: 
Chemoprevention, curcumin, NF-êB, apoptosis, ROS, ceramide.
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