Peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) ligands inhibit growth of UACC903 and MCF7 human cancer cell lines

Elizabeth E. Girroir, Holly E. Hollingshead, Andrew N. Billin, Timothy M. Willson, Gavin Robertson, Arun Sharma, Shantu Amin, Frank J. Gonzalez, Jeffrey Maurice Peters

Research output: Contribution to journalArticle

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Abstract

The development of peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) ligands for the treatment of diseases including metabolic syndrome, diabetes and obesity has been hampered due to contradictory findings on their potential safety. For example, while some reports show that ligand activation of PPARβ/δ promotes the induction of terminal differentiation and inhibition of cell growth, other reports suggest that PPARβ/δ ligands potentiate tumorigenesis by increasing cell proliferation. Some of the contradictory findings could be due in part to differences in the ligand examined, the presence or absence of serum in cell cultures, differences in cell lines or differences in the method used to quantify cell growth. For these reasons, this study examined the effect of ligand activation of PPARβ/δ on cell growth of two human cancer cell lines, MCF7 (breast cancer) and UACC903 (melanoma) in the presence or absence of serum using two highly specific PPARβ/δ ligands, GW0742 or GW501516. Culturing cells in the presence of either GW0742 or GW501516 caused upregulation of the known PPARβ/δ target gene angiopoietin-like protein 4 (ANGPTL4). Inhibition of cell growth was observed in both cell lines cultured in the presence of either GW0742 or GW501516, and the presence or absence of serum had little influence on this inhibition. Results from the present studies demonstrate that ligand activation of PPARβ/δ inhibits the growth of both MCF7 and UACC903 cell lines and provide further evidence that PPARβ/δ ligands are not mitogenic in human cancer cell lines.

Original languageEnglish (US)
Pages (from-to)236-243
Number of pages8
JournalToxicology
Volume243
Issue number1-2
DOIs
StatePublished - Jan 14 2008

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Peroxisome Proliferator-Activated Receptors
Cells
Ligands
Cell Line
Cell growth
Growth
Neoplasms
Chemical activation
Serum
Angiopoietins
Metabolic Diseases
MCF-7 Cells
Cell proliferation
Medical problems
Cell culture
Cell Differentiation
Melanoma
Carcinogenesis
Up-Regulation
Cell Culture Techniques

All Science Journal Classification (ASJC) codes

  • Toxicology

Cite this

Girroir, Elizabeth E. ; Hollingshead, Holly E. ; Billin, Andrew N. ; Willson, Timothy M. ; Robertson, Gavin ; Sharma, Arun ; Amin, Shantu ; Gonzalez, Frank J. ; Peters, Jeffrey Maurice. / Peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) ligands inhibit growth of UACC903 and MCF7 human cancer cell lines. In: Toxicology. 2008 ; Vol. 243, No. 1-2. pp. 236-243.
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Peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) ligands inhibit growth of UACC903 and MCF7 human cancer cell lines. / Girroir, Elizabeth E.; Hollingshead, Holly E.; Billin, Andrew N.; Willson, Timothy M.; Robertson, Gavin; Sharma, Arun; Amin, Shantu; Gonzalez, Frank J.; Peters, Jeffrey Maurice.

In: Toxicology, Vol. 243, No. 1-2, 14.01.2008, p. 236-243.

Research output: Contribution to journalArticle

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T1 - Peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) ligands inhibit growth of UACC903 and MCF7 human cancer cell lines

AU - Girroir, Elizabeth E.

AU - Hollingshead, Holly E.

AU - Billin, Andrew N.

AU - Willson, Timothy M.

AU - Robertson, Gavin

AU - Sharma, Arun

AU - Amin, Shantu

AU - Gonzalez, Frank J.

AU - Peters, Jeffrey Maurice

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N2 - The development of peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) ligands for the treatment of diseases including metabolic syndrome, diabetes and obesity has been hampered due to contradictory findings on their potential safety. For example, while some reports show that ligand activation of PPARβ/δ promotes the induction of terminal differentiation and inhibition of cell growth, other reports suggest that PPARβ/δ ligands potentiate tumorigenesis by increasing cell proliferation. Some of the contradictory findings could be due in part to differences in the ligand examined, the presence or absence of serum in cell cultures, differences in cell lines or differences in the method used to quantify cell growth. For these reasons, this study examined the effect of ligand activation of PPARβ/δ on cell growth of two human cancer cell lines, MCF7 (breast cancer) and UACC903 (melanoma) in the presence or absence of serum using two highly specific PPARβ/δ ligands, GW0742 or GW501516. Culturing cells in the presence of either GW0742 or GW501516 caused upregulation of the known PPARβ/δ target gene angiopoietin-like protein 4 (ANGPTL4). Inhibition of cell growth was observed in both cell lines cultured in the presence of either GW0742 or GW501516, and the presence or absence of serum had little influence on this inhibition. Results from the present studies demonstrate that ligand activation of PPARβ/δ inhibits the growth of both MCF7 and UACC903 cell lines and provide further evidence that PPARβ/δ ligands are not mitogenic in human cancer cell lines.

AB - The development of peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) ligands for the treatment of diseases including metabolic syndrome, diabetes and obesity has been hampered due to contradictory findings on their potential safety. For example, while some reports show that ligand activation of PPARβ/δ promotes the induction of terminal differentiation and inhibition of cell growth, other reports suggest that PPARβ/δ ligands potentiate tumorigenesis by increasing cell proliferation. Some of the contradictory findings could be due in part to differences in the ligand examined, the presence or absence of serum in cell cultures, differences in cell lines or differences in the method used to quantify cell growth. For these reasons, this study examined the effect of ligand activation of PPARβ/δ on cell growth of two human cancer cell lines, MCF7 (breast cancer) and UACC903 (melanoma) in the presence or absence of serum using two highly specific PPARβ/δ ligands, GW0742 or GW501516. Culturing cells in the presence of either GW0742 or GW501516 caused upregulation of the known PPARβ/δ target gene angiopoietin-like protein 4 (ANGPTL4). Inhibition of cell growth was observed in both cell lines cultured in the presence of either GW0742 or GW501516, and the presence or absence of serum had little influence on this inhibition. Results from the present studies demonstrate that ligand activation of PPARβ/δ inhibits the growth of both MCF7 and UACC903 cell lines and provide further evidence that PPARβ/δ ligands are not mitogenic in human cancer cell lines.

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