Anticancer Effect of a Curcumin Derivative B63: ROS Production and Mitochondrial Dysfunction.

Anticancer Effect of a Curcumin Derivative B63: ROS Production and Mitochondrial Dysfunction. Curr Cancer Drug Targets. 2013 Nov 25; Authors: Zheng A, Li H, Wang X, Feng Z, Xu J, Cao K, Zhou B Abstract Curcumin, a polyphenol isolated from the plant Curcuma longa, displays chemotherapeutic and chemopreventive effects in diverse cancers, including colorectal cancer. A mono-carbonyl analogue B63 was synthesized through several chemical modifications of the basic structure of curcumin to increase its biological activity and bioavailability. In vitro assays showed potent anti- proliferative effects of B63 on colon cancer cells (about 2 fold more effective than curcumin based on IC50). B63 treatment also induced significant necrosis, apoptosis and S phase cell cycle arrest in SW620 colon cancer cells. The pro-apoptotic proteins Bad and Bim were up-regulated, and cytochrome c release from the mitochondria into the cytosol was enhanced, resulting in pro-caspase-3 and PARP-1 cleavage. Furthermore, the anticancer activity of B63 was dependent on intracellular ROS from damaged mitochondrial function and induced endoplasmic reticulum (ER) stress. In vivo, 50 mg/kg of B63 inhibit tumor growth similarly to 100 mg/kg curcumin in a mouse xenograft model using SW620 cells. These results suggest that the curcumin derivative B63 has a greater anti-cancer capacity than the parent curcumin in colon cancer cells and that the necrotic and apoptotic effects of B63 ar...
Source: Current Cancer Drug Targets - Category: Cancer & Oncology Authors: Tags: Curr Cancer Drug Targets Source Type: research