QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: jpet.103.049098v1 305/3/932    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Laurora, S. Articles by Barrera, G. Search for Related Content PubMed PubMed Citation Articles by Laurora, S. Articles by Barrera, G.

CELLULAR AND MOLECULAR

Peroxisome Proliferator-Activated Receptor Ligands Affect Growth-Related Gene Expression in Human Leukemic Cells

Departments of Medicine and Experimental Oncology (S.L., S.P., F.B., A.F., M.M., P.R., M.U.D., G.B.) and Anatomy, Pharmacology, and Forensic Medicine (C.F.), University of Turin, Turin, Italy

Peroxisome proliferator-activated receptors (PPARs) are ligand-activated nuclear receptors. Three subtypes of PPARs (, , and ) have been identified in different tissues. PPAR and PPAR ligands inhibit cell proliferation and induce differentiation in several human cell models. We demonstrated that both PPAR (clofibrate and ciprofibrate) and PPAR ligands (troglitazone and 15 deoxy-prostaglandin J2, 15d-PGJ2) inhibited growth, induced the onset of monocytic-like differentiation, and increased the proportion of G₀/G₁ cells in the HL-60 leukemic cell line. Moreover, 3 days after the treatment with 2.5 µM 15d-PGJ2, an increase in sub-G₀/G₁ population occurred, compatible with an induction of programmed cell death. To clarify the mechanisms involved in HL-60 growth inhibition due to the effects of PPAR ligands, we investigated their action on the expression of some genes involved in the control of cell proliferation, differentiation, and cell cycle progression such as c-myc, c-myb, and cyclin D1 and D2. Clofibrate (50 µM), ciprofibrate (50 µM), and 15d-PGJ2 (2.5 µM) inhibited c-myb and cyclin D2 expression, whereas they did not affect c-myc and cyclin D1 expression. Only troglitazone (5 µM) decreased c-myc mRNA and protein levels, besides decreasing c-myb and cyclin D2. The down-regulations of c-myb and cyclin D2 expression represent the first evidence of the inhibitory effect exerted by PPAR ligands on these genes. Moreover, the inhibition of c-myc expression by troglitazone may depend on a PPAR-independent mechanism.

Address correspondence to: Prof. Giuseppina Barrera, Dipartimento di Medicina e Oncologia Sperimentale, Sezione di Patologia Generale, Corso Raffaello, 30; 10125 Torino, Italy. E-mail: giuseppina.barrera{at}unito.it

This article has been cited by other articles:

				M. Schwab, V. Reynders, S. Loitsch, Y. M. Shastri, D. Steinhilber, O. Schroder, and J. Stein PPAR{gamma} is involved in mesalazine-mediated induction of apoptosis and inhibition of cell growth in colon cancer cells Carcinogenesis, July 1, 2008; 29(7): 1407 - 1414. [Abstract] [Full Text] [PDF]

				V. Y. Ng, C. Morisseau, J. R. Falck, B. D. Hammock, and D. L. Kroetz Inhibition of Smooth Muscle Proliferation by Urea-Based Alkanoic Acids via Peroxisome Proliferator-Activated Receptor {alpha}-Dependent Repression of Cyclin D1 Arterioscler. Thromb. Vasc. Biol., November 1, 2006; 26(11): 2462 - 2468. [Abstract] [Full Text] [PDF]

				H. Liu, C. Zang, M. H. Fenner, D. Liu, K. Possinger, H. P. Koeffler, and E. Elstner Growth inhibition and apoptosis in human Philadelphia chromosome-positive lymphoblastic leukemia cell lines by treatment with the dual PPAR{alpha}/{gamma} ligand TZD18 Blood, May 1, 2006; 107(9): 3683 - 3692. [Abstract] [Full Text] [PDF]

				J. Banerjee and C. M Komar Effects of luteinizing hormone on peroxisome proliferator-activated receptor {gamma} in the rat ovary before and after the gonadotropin surge Reproduction, January 1, 2006; 131(1): 93 - 101. [Abstract] [Full Text] [PDF]

				B. Martinez, A. Perez-Castillo, and A. Santos The mitochondrial respiratory complex I is a target for 15-deoxy-{Delta}12,14-prostaglandin J2 action J. Lipid Res., April 1, 2005; 46(4): 736 - 743. [Abstract] [Full Text] [PDF]

				R. Piva, P. Gianferretti, A. Ciucci, R. Taulli, G. Belardo, and M. G. Santoro 15-Deoxy-{Delta}12,14-prostaglandin J2 induces apoptosis in human malignant B cells: an effect associated with inhibition of NF-{kappa}B activity and down-regulation of antiapoptotic proteins Blood, February 15, 2005; 105(4): 1750 - 1758. [Abstract] [Full Text] [PDF]