PPAR gamma Activation Extinguishes Smoking Carcinogen by Inhibiting NNK-Mediated Proliferation
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摘要Among the carcinogenic chemicals of cigarette smoking, 4-(methylnitrosamino-1-(3-pyridyl)-1-butanone (NNK) is the most potent. The activation of peroxisome proliferator-activated receptor (PPAR)gamma can arrest the growth of lung cancer. We hypothesized that PPAR gamma activation inhibits NNK-mediated proliferation of lung cancer cells. PPAR gamma expression was increased in 94.7% human lung cancer tumor tissues, compared with their paired corresponding nontumor tissues. PPAR gamma was also found to be abundant in all the lung cancer cell lines tested. Troglitazone dose-dependently inhibited the NNK-mediated proliferation of lung cancer cells that expressed PPAR gamma. Troglitazone blocked NNK-induced up-regulation of HO-1, Bcl-2, and c-IAP2, and recovered Bad activity that was suppressed by NNK. NNK promoted the nuclear p21, whereas troglitazone increased cytosolic p21. Troglitazone increased PPAR gamma transcriptional activity in NNK-treated cells and a PPAR gamma dominant-negative inhibitor completely suppressed the action of troglitazone, indicating that troglitazone against NNK was PPAR gamma-dependent. The findings reveal a novel molecular pathway of PPAR gamma activation against cigarette smoking-related lung cancer.
著者Li MY, Hsin MKY, Yip J, Mok TSK, Underwood MJ, Chen GG
期刊名稱American Journal of Respiratory Cell and Molecular Biology
詳細描述To ORKTS: Article in press
出版年份2010
月份1
日期1
卷號42
期次1
出版社AMER THORACIC SOC
頁次113 - 122
國際標準期刊號1044-1549
電子國際標準期刊號1535-4989
語言英式英語
關鍵詞HO-1; NF-kappa B; NNK; p21; PPAR gamma; troglitazone
Web of Science 學科類別Biochemistry & Molecular Biology; BIOCHEMISTRY & MOLECULAR BIOLOGY; Cell Biology; CELL BIOLOGY; Respiratory System; RESPIRATORY SYSTEM

上次更新時間 2020-28-10 於 00:56