Antitumor effects of emodin on LS1034 human colon cancer cells in vitro and in vivo: Roles of apoptotic cell death and LS1034 tumor xenografts model

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• 作者：Yi-Shih Ma^a ; ^b ; Shu-Wen Weng^a ; ^c ; Meng-Wei Lin^d ; Chi-Cheng Lu^e ; Jo-Hua Chiang^e ; Jai-Sing Yang^f ; Kuang-Chi Lai^g ; ^h ; Jing-Pin Linⁱ ; Nou-Ying Tangⁱ ; Jaung-Geng Lin^a ; ^{jglin@mail.cmu.edu.tw} ; Jing-Gung Chung^d ; ⁱ ; ^{jgchung@mail.cmu.edu.tw}
• 关键词：螖唯m ; mitochondrial membrane potential ; AIF ; apoptosis-inducing factor ; Bax ; Bcl-2-associated X protein ; Bcl-2 ; B-cell lymphoma 2 ; DAPI ; 4 ; 6-diamidino-2-phenylindole dihydrochloride ; DMSO ; dimethyl sulfoxide ; Endo G ; endonuclease G ; DCFH-DA ; 2&prime ; 7&p
• 刊名：Food and Chemical Toxicology
• 出版年：2012
• 期刊代码：20_02786915
• 类别：pha
• 出版时间：May, 2012
• 卷：50
• 期：5
• 页码：1271-1278
• 文件大小：1089 K

摘要

Emodin, an active natural anthraquinone derivative, is found in the roots and rhizomes of numerous Chinese medicinal herbs and exhibits anticancer effects on many types of human cancer cell lines. The aim of this study investigated that emodin induced apoptosis of human colon cancer cells (LS1034) in vitro and inhibited tumor nude mice xenografts bearing LS1034 in vivo. In in vitro study, emodin induced cell morphological changes, decreased the percentage of viability, induced G2/M phase arrest and increased ROS and Ca²⁺ productions as well as loss of mitochondrial membrane potential (螖唯_m) in LS1034 cells. Emodin-triggered apoptosis was also confirmed by DAPI staining and these effects are concentration-dependent. Western blot analysis indicated that the protein levels of cytochrome c, caspase-9 and the ratio of Bax/Bcl-2 were increased in LS1034 cells after emodin exposure. Emodin induced the productions of ROS and Ca²⁺ release, and altered anti- and pro-apoptotic proteins, leading to mitochondrial dysfunction and activations of caspase-9 and caspase-3 for causing cell apoptosis. In in vivo study, emodin effectively suppressed tumor growth in tumor nude mice xenografts bearing LS1034. Overall, the potent in vitro and in vivo antitumor activities of emodin suggest that it might be developed for treatment of colon cancer in the future.