Tangeretin derivative, 5-acetyloxy-6,7,8,4'-tetramethoxyflavone induces G2/M arrest, apoptosis and autophagy in human non-small cell lung cancer cells in vitro and in vivo

in Sciences Citation Index(SCI), 科學引文索引資料庫(SCI)
標題Tangeretin derivative, 5-acetyloxy-6,7,8,4'-tetramethoxyflavone induces G2/M arrest, apoptosis and autophagy in human non-small cell lung cancer cells in vitro and in vivo
出版類型SCI(Sciences Citation Index)
出版年度2016
AuthorsYi-Rong Li, 李宜蓉, Shiming Li 李世明, Chi-Tang Ho 何其儻, Ya-Han Chang 張雅涵, Kok-Tong Tan 陳國棟, Ting-Wen Chung 鍾婷雯, Bing-Yen Wang 王秉彥, Yu-Kuo Chen 陳與國, & Chi-Chen Lin 林季千
開始頁48
頁數16
出版日期2016 / 1
其他編號0000
中文摘要

Tangeretin, a major phytochemicals in tangerine peels--an important Chinese herb, has been found to have anti-carcinogenic properties. To improve bioavailability and increase potency of tangeretin, its derivative, 5-acetyloxy-6,7,8,4'-tetramethoxyflavone (5-AcTMF), has been synthesized and shown potent inhibition of proliferation activity against human breast and leukemia cancer cell lines. In this study, we have further investigated the anticancer effects of 5-AcTMF on CL1-5 non-small cell lung cancer cells (NSCLC) both in vitro and in vivo and demonstrated that 5-AcTMF effectively inhibited cancer cell proliferation, induced G2/M-phase arrest associated with cdc2 and CDC25c and increased in the apoptotic cells associated with caspase activation, down regulation of Bcl-2, XIAP and Survivn, inducing release of cytochrome c into the cytosol and disruption of mitochondrial membrane potential. We also found that 5-AcTMF treatment of CL1-5 activated autophagy, indicated by triggered autophagosome formation and increased LC3-II levels and formation of LC3 puncta. Moreover, we also found that 5-AcTMF lowered phophoatidylinositol 3-kinase/AKT/mTOR signaling pathway. Over-expression of AKT by AKT cDNA transfection decreased 5-AcTMF mediated apoptosis and autophagy, supporting the induction of apoptosis and autophagy by inhibition of AKT pathway. In an animal study, 5-AcTMF effectively delayed tumor growth in a nude mouse model of CL1-5 xenografts without observed adverse effect. Immunohistochemistry Analysis indicated that 5-AcTMF induced CL1-5 cell apoptosis and autophagy in vivo. Taken together, these data demonstrate that 5-AcTMF is a novel small molecule agent that can inhibit NSCLC cell proliferation, and induce G(2)/M phase arrest and via the mitochondrial apoptotic pathway and autophagy.

網址https://www.tandfonline.com/doi/full/10.1080/15384047.2015.1108491
期刊名稱Cancer Biology & Therapy
校址:912 屏東縣內埔鄉學府路1號 總機:886-8-7703202 傳真:886-8-7740165 系統開發統維護單位:國立屏東科技大學 電算中心 版權所有