title: Troglitazone, a PPAR agonist, inhibits human prostate cancer cell growth through inactivation of NFκB via suppression of GSK-3β expression.
abstract: PPARγ ligands have been reported to reduce proliferation of human prostate cancer cells. However, the molecular mechanism of PPARγ agonist-induced cell growth inhibition of prostate cancer cells is not clear. GSK-3β expression and NFκB activity have important roles in prostate cancer development. To investigate the mechanisms of the PPARγ agonist-induced prostate cancer cell growth inhibition, we examined the effect of troglitazone on the expression of PPARγ, GSK-3β and activity of NFκB as well as on the prostate cancer cell growth. Troglitazone induced the expression of PPARγ in the nuclear of PC-3 cells, but not in LNCaP cells. Troglitazone (0-16 uM) inhibited cancer cell growth in a similar extend between both cells accompanied by the induction of cell cycle arrest in G(0)/G(1) phase and an increased in the similar extent of apoptotic cell death in concentration dependent manner. Troglitazone inhibited the constitutive expression of GSK-3β and activation of NFκB. Co-treatment of troglitazone with a GSK-3β inhibitor (AR-a014418) or GSK-3β siRNA significantly augmented the inhibitory effect of troglitazone on the NFκB activity and on prostate cancer cell growth inhibition and apoptotic cell death. However, overexpression of GSK-3β hindered troglitazone-induced cell growth inhibition and NFκB inactivation. These results suggest that PPARγ agonist, troglitazone, inhibits prostate cancer cell growth through inactivation of NFκB via suppression of GSK-3β expression.
authors: College of Pharmacy and Medical Research Center, Chungbuk National University, Korea.
authors: Jung Ok
authors: JO
authors: Ban
authors: Ju Hoon
authors: JH
authors: Oh
authors: Seung Mo
authors: SM
authors: Son
authors: Dohee
authors: D
authors: Won
authors: Ho Seub
authors: HS
authors: Song
authors: Sang Bae
authors: SB
authors: Han
authors: Dong Cheul
authors: DC
authors: Moon
authors: Keon Wook
authors: KW
authors: Kang
authors: Min Jong
authors: MJ
authors: Song
authors: Jin Tae
authors: JT
authors: Hong