PPAR gamma Activation Extinguishes Smoking Carcinogen by Inhibiting NNK-Mediated Proliferation
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AbstractAmong 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.
All Author(s) ListLi MY, Hsin MKY, Yip J, Mok TSK, Underwood MJ, Chen GG
Journal nameAmerican Journal of Respiratory Cell and Molecular Biology
Detailed descriptionTo ORKTS: Article in press
Volume Number42
Issue Number1
Pages113 - 122
LanguagesEnglish-United Kingdom
KeywordsHO-1; NF-kappa B; NNK; p21; PPAR gamma; troglitazone
Web of Science Subject CategoriesBiochemistry & Molecular Biology; BIOCHEMISTRY & MOLECULAR BIOLOGY; Cell Biology; CELL BIOLOGY; Respiratory System; RESPIRATORY SYSTEM

Last updated on 2020-30-11 at 01:39