%0 Journal Article
%T Anaphase-promoting complex/cyclosome protein Cdc27 is a target for curcumin-induced cell cycle arrest and apoptosis
%A Seung Joon Lee
%A Sigrid A Langhans
%J BMC Cancer
%D 2012
%I BioMed Central
%R 10.1186/1471-2407-12-44
%X Cell cycle profiles were determined in control and curcumin-treated medulloblastoma and various other cancer cell lines. Pull-down assays were used to confirm curcumin binding. APC/C activity was determined using an in vitro APC activity assay.We identified Cdc27/APC3, a component of the APC/C, as a novel molecular target of curcumin and showed that curcumin binds to and crosslinks Cdc27 to affect APC/C function. We further provide evidence that curcumin preferably induces apoptosis in cells expressing phosphorylated Cdc27 usually found in highly proliferating cells.We report that curcumin directly targets the SAC to induce apoptosis preferably in cells with high levels of phosphorylated Cdc27. Our studies provide a possible molecular mechanism why curcumin induces apoptosis preferentially in cancer cells and suggest that phosphorylation of Cdc27 could be used as a biomarker to predict the therapeutic response of cancer cells to curcumin.Curcumin, or diferuloylmethane, is a hydrophobic polyphenol derived from the rhizome of the herb Curcuma longa. It is better known as the yellow pigment in the widely used Asian spice turmeric. Recently, curcumin gained attention as an anti-cancer agent because of its chemopreventive and chemotherapeutic potential while having no discernable side effects. Curcumin induces apoptosis in various tumor cells and can prevent tumor initiation and growth in carcinogen-induced rodent models as well as in subcutaneous and orthotopic tumor xenografts [1-3]. Although it is still not known why curcumin preferentially kills tumor cells, it has been identified as one of the major natural agents that inhibit tumor initiation and tumor promotion.Curcumin inhibits the proliferation of a wide variety of cancer cells including breast, blood, colon, liver, pancreas, kidney, prostate, and skin [1,2]. We and others have shown that it induces cell death in medulloblastoma, the most common pediatric brain tumor [3-5], and inhibits tumor growth in in vivo m
%U http://www.biomedcentral.com/1471-2407/12/44