title: Anticancer effect of a curcumin derivative B63: ROS production and mitochondrial dysfunction.
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 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.
authors.forename: Adi
authors.initials: A
authors.lastname: Zheng
authors.forename: Hao
authors.initials: H
authors.lastname: Li
authors.forename: Xun
authors.initials: X
authors.lastname: Wang
authors.forename: Zhihui
authors.initials: Z
authors.lastname: Feng
authors.forename: Jie
authors.initials: J
authors.lastname: Xu
authors.forename: Ke
authors.initials: K
authors.lastname: Cao
authors.forename: Bo
authors.initials: B
authors.lastname: Zhou
authors.forename: Jing
authors.initials: J
authors.lastname: Wu
authors.affiliation: Institute of Mitochondrial Biology and Medicine, Xi'an Jiaotong University School of Life Science and Technology, Xi'an 710049, China. j.liu@mail.xjtu.edu.cn.
authors.forename: Jiankang
authors.initials: J
authors.lastname: Liu
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D003474:Curcumin / Q000031:analogs & derivatives / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D005260:Female; D045325:HCT116 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D009336:Necrosis; D018384:Oxidative Stress / Q000187:drug effects*; D008517:Phytotherapy; D010946:Plants, Medicinal; D017382:Reactive Oxygen Species / Q000378:metabolism*; D059807:S Phase Cell Cycle Checkpoints / Q000187:drug effects; D013997:Time Factors; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D017382:Reactive Oxygen Species; D003474:Curcumin