Anticancer Effect of a Curcumin Derivative B63: ROS Production and Mitochondrial Dysfunction
Adi Zheng, Hao Li, Xun Wang, Zhihui Feng, Jie Xu, Ke Cao, Bo Zhou, Jing Wu and Jiankang Liu
Affiliation: Institute of Mitochondrial Biology and Medicine, Xi’an Jiaotong University School of Life Science and Technology, Xi’an 710049, China.
Keywords: Colon cancer cells, curcumin, curcumin derivative, ER stress, mitochondrial dysfunction, ROS.
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 anticancer
capacity than the parent curcumin in colon cancer cells and that the necrotic and apoptotic effects of B63 are
mediated by ROS resulting from ER stress and mitochondrial dysfunction.
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