Anticancer efficacy of 5F in NNK-induced lung cancer development of A/J mice and human lung cancer cells
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摘要The mechanism responsible for the apoptotic effect induced by ent-11 alpha-hydroxy-15-oxo-kaur-16-en-19-oic-acid (5F) is not fully understood and its in vivo effect has not been tested. In this study, the effect and mechanism of 5F was investigated in cigarette smoking carcinogen 4-methylnitrosamino-1-3-pyridyl-butanone (NNK)-induced mouse lung tumor model and in cultured lung cancer cells NCI-H23 and CRL-2066. 5F were given to mice after they were treated with NNK for 18 weeks. The effect of 5F on the lung tumor formation was examined, and its side effect was monitored. Cell proliferation and apoptosis were determined through expression of PCNA, Bcl-2, Bax, and TUNEL assay in in vivo animal model. 5F significantly inhibited the NNK-induced lung tumors by inducing apoptosis and suppressing cell proliferation in vivo with minimal side effects. Cell culture experiments showed that 5F translocated Bax into the mitochondria, downregulated Bcl-2, activated caspase-9 and caspase-3, released cytochrome c into the cytosol, and translocated AIF from the mitochondria to the nucleus, which leading to G2-M cell cycle arrest and cell apoptosis. 5F also activated ERK1/2 and the inhibition of ERK1/2 suppressed 5F-mediated changes in apoptotic molecules. In addition to ERK1/2, 5F activated Akt. The inhibition of Akt further facilitated the apoptosis induced, suggesting that Akt activation was anti-apoptotic rather than pro-apoptotic. Collectively, 5F is effective against lung cancer in vivo with minimal side effects. It induces apoptosis in lung cancer through the mitochondrial-mediated pathway, in which the activation of ERK is critical.
著者Li MY, Leung J, Kong AWY, Liang NC, Wu KF, Hsin MKY, Deng YF, Gong XL, Lv YN, Mok TSK, Underwood MJ, Chen GG
期刊名稱Journal of Molecular Medicine
出版年份2010
月份12
日期1
卷號88
期次12
出版社SPRINGER
頁次1265 - 1276
國際標準期刊號0946-2716
電子國際標準期刊號1432-1440
語言英式英語
關鍵詞5F; Apoptosis; Lung cancer; Mitochondria; NNK
Web of Science 學科類別Genetics & Heredity; GENETICS & HEREDITY; Medicine, Research & Experimental; MEDICINE, RESEARCH & EXPERIMENTAL; Research & Experimental Medicine

上次更新時間 2020-15-09 於 00:43