Phorbol ester potentiates the growth inhibitory effects of troglitazone via up-regulation of PPAR{gamma} in A549 cells
- Department of Pharmacology, Gyeongsang Institute of Health Science, College of Medicine, Gyeongsang National University, Jinju 660-751 (Korea, Republic of)
- Division of Applied Life Science, College of Agriculture and Life, Gyeongsang National University, Jinju 660-701 (Korea, Republic of)
- Department of Animal Science and Biotechnology, Konkuk University, Seoul 143-701 (Korea, Republic of)
The activation of peroxisome proliferator-activated receptor gamma (PPAR{gamma}) has been shown to induce growth arrest and differentiation of various cancer cells. In the current study, we investigated the effect of 12-O-tetradecanoylphorbol-13-acetate (TPA) on the expression of PPAR{gamma} and proliferation of A549 cells. TPA elicited a dose- and time-dependent increase in PPAR{gamma} mRNA and protein levels. PPAR{gamma} expression in response to TPA was attenuated by pretreatment with bisindolylmaleimide I, N-acetyl-L-cysteine (NAC) and PD98059. TPA-induced protein kinase C (PKC) activation was linked to the generation of reactive oxygen species (ROS), both of which were indispensable for PPAR{gamma} expression in A549 cells. Pretreatment with bisindolylmaleimide I or NAC blocked TPA-induced phosphorylation of extracellular signal-regulated kinase (ERK), suggesting that ERK-mediated signaling is also involved in the induction of PPAR{gamma}. Furthermore, the growth inhibitory effect of troglitazone was significantly potentiated by prolonged incubation with TPA and was attenuated in the presence of GW9662, a specific inhibitor of PPAR{gamma}. These effects were associated with an induction of cell cycle arrest at G /G{sub 1} phase, which was accompanied by the induction of p21{sup Waf1/Cip1} expression and decreased cyclin D1 expression. Taken together, these observations indicate that TPA synergizes with PPAR{gamma} ligand to inhibit cell growth through up-regulation of PPAR{gamma} expression.
- OSTI ID:
- 20854526
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 349, Issue 2; Other Information: DOI: 10.1016/j.bbrc.2006.08.085; PII: S0006-291X(06)01885-7; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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