Description
Troglitazone is a thiazolidinedione PPARγ agonist that exhibits anti-diabetic, anticancer, anti-fibrotic, and anti-inflammatory activities. Troglitazone contains a vitamin E-like ring structure that forms hepatotoxic metabolites in vivo. Troglitazone induces apoptosis in cervical cancer cells and decreases expression and activity of telomerase in ER- breast cancer cells. In vitro, troglitazone activates AMPK, decreases membrane potential, inhibits high glucose-closed ATP-sensitive K+ channels, and decreases insulin hypersecretion. In alveolar epithelial cells, troglitazone inhibits TGF-β1-induced activation of Akt, GSK-3β and Smad2/3, decreases β-catenin signaling, and suppresses epithelial-to-mesenchymal transition (EMT). Additionally, this compound inhibits PAM-induced increases in TGF-β1 and increases MUC1 expression in airway epithelial cells.
References
Chen HM, Zhang DG, Wu JX, et al. Ubiquitination of p53 is involved in troglitazone induced apoptosis in cervical cancer cells. Asian Pac J Cancer Prev. 2014;15(5):2313-8. PMID: 24716976.
Deng R, Nie A, Jian F, et al. Acute exposure of beta-cells to troglitazone decreases insulin hypersecretion via activating AMPK. Biochim Biophys Acta. 2014 Jan;1840(1):577-85. PMID: 24144566.
Zhou B, Buckley ST, Patel V, et al. Troglitazone attenuates TGF-β1-induced EMT in alveolar epithelial cells via a PPARγ-independent mechanism. PLoS One. 2012;7(6):e38827. PMID: 22745681.
Park YS, Lillehoj EP, Kato K, et al. PPARγ inhibits airway epithelial cell inflammatory response through a MUC1-dependent mechanism. Am J Physiol Lung Cell Mol Physiol. 2012 Apr 1;302(7):L679-87. PMID: 22268120.
Rashid-Kolvear F, Taboski MA, Nguyen J, et al. Troglitazone suppresses telomerase activity independently of PPARgamma in estrogen-receptor negative breast cancer cells. BMC Cancer. 2010 Jul 22;10:390. PMID: 20650001.
Ozaki S, Minamisono T, Yamashita T, et al. Supersaturation-nucleation behavior of poorly soluble drugs and its impact on the oral absorption of drugs in thermodynamically high-energy forms. J Pharm Sci. 2012 Jan;101(1):214-222. PMID: 21918988.
