标题：Acetyl-11-keto-beta-boswellic acid (AKBA) prevents human colonic adenocarcinoma growth through modulation of multiple signaling pathways
作者机构：[Yuan, Y] Department of Pharmacology, School of Pharmaceutical Sciences, Shandong University, Jinan, China;[ Cui, S.-X] Center for Food and Drugs Eval 更多
通讯作者地址：[Gao, ZH]McGill Univ, Dept Pathol, Montreal, PQ, Canada.
来源：Biochimica et Biophysica Acta. General Subjects
关键词：Acetyl-11-keto-beta-boswellic acid (AKBA);Anti-inflammation;Apoptosis;Aspirin;Colon adenocarcinoma;Toxicity
摘要：Background Acetyl-11-keto-beta-boswellic acid (AKBA) is a derivative of boswellic acid. We have previously reported that AKBA can reduce the number and size of colonic adenomatous polyps in the APCMin/+ mouse model. In this study, we evaluated the effect of AKBA on human colonic adenocarcinoma growth. Its efficacy and toxicity were compared with those of the non-steroidal anti-inflammatory drug aspirin. Methods The inhibition of cancer cell growth was estimated by colorimetric and clonogenic assay. Cell cycle distribution was analyzed by the flow cytometry assay. Annexin V-FITC/PI staining and JC-1 fluorescence probe assays were performed to determine the apoptotic cells. Further experiment was carried out in mice with HT-29 xenografts. AKBA was orally administered for 24 days. The HT-29 xenografts were removed for TUNEL staining and western blotting analysis. Blood was obtained for clinical chemical analysis, and samples of organs were sectioned for microscopic assessment. Results AKBA significantly inhibited human colon adenocarcinoma growth, showing arrest of the cell cycle in G1-phase and induction of apoptosis. AKBA administration in mice effectively delayed the growth of HT-29 xenografts without signs of toxicity. The activity of AKBA was more potent than that of aspirin. Western blotting suggested that this activity may arise from its multiple effects on the activation of apoptotic proteins, suppression of inflammatory cytokines and modulation of EGFR and ATM/P53 signaling pathways in the HT-29 xenografts. Conclusions AKBA prevents the growth of colonic adenocarcinoma through modulation of multiple signaling pathways. General significance AKBA could be a promising agent in the prevention of colonic adenocarcinomas.