Curcumin is a non-competitive and selective inhibitor of phosphorylase kinase.
Recently, we reported that curcumin (diferuloylmethane) inhibits the growth of several different kinds of tumor cells. In order to investigate the mechanism of this inhibition, we examined the effects of curcumin on different protein kinases: highly purified protein kinase A (PkA), protein kinase C (PkC), protamine kinase (cPK), phosphorylase kinase (PhK), autophosphorylation-activated protein kinase (AK) and pp60c-src tyrosine kinase. While all kinases tested were inhibited by curcumin, only PhK was completely inhibited at relatively lower concentrations. At around 0.1 mM curcumin, PhK, pp60c-src, PkC, PkA, AK, and cPK were inhibited by 98%, 40%, 15%, 10%, 1%, and 0.5%, respectively. Lineweaver-Burk plot analysis indicated that curcumin is a non-competitive inhibitor of PhK with a Ki of 0.075 mM. Overall, our results indicate that curcumin is a potent and selective inhibitor of phosphorylase kinase, a key regulatory enzyme involved in the metabolism of glycogen. This has important implications for the anti-proliferative effects of curcumin.
Reddy
S
S
Department of Clinical Immunology and Biological Therapy, University of Texas M.D. Anderson Cancer Center, Houston 77030.
Aggarwal
B B
BB
D001667:Binding, Competitive; D003474:Curcumin / Q000494:pharmacology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000187:drug effects; D015394:Molecular Structure; D010764:Phosphorylase Kinase / Q000037:antagonists & inhibitors*; D010766:Phosphorylation; D006656:Protamine Kinase / Q000187:drug effects; D011493:Protein Kinase C / Q000187:drug effects; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000187:drug effects
D010764:Phosphorylase Kinase; D016392:Proto-Oncogene Proteins pp60(c-src); D006656:Protamine Kinase; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D003474:Curcumin