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Mol Carcinog. 2014 Sep;53(9):753-63. doi: 10.1002/mc.22029. Epub 2013 Apr 26.

Differential effects on lung cancer cell proliferation by agonists of glucocorticoid and PPARα receptors.

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1
Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, Texas; Medical Research Division, Regional Academic Health Center at Edinburg, University of Texas Health Science Center at San Antonio, Edinburg, Texas.

Abstract

Glucocorticoids (GCs) are well-known anti-inflammatory compounds, but they also inhibit cell proliferation depending on cell type. Similarly, peroxisome proliferator-activated receptors (PPARα, PPARδ, and PPARγ) also possess anti-proliferation properties beyond their canonical roles as metabolic mediators. In the present study, we investigated the potential additive or synergistic inhibitory effects on cancer cell proliferation by simultaneous application of fenofibrate and budesonide, agonists for PPARα and glucocorticoid receptor, respectively. We observed differential effects on cell proliferation in A549 and SK-MES-1 lung cancer cells by budesonide and fenofibrate. Fenofibrate inhibited cell proliferation in both TP53 wild type and deficient lung cancer cells. The anti-proliferation effect of budesonide in TP53 wild type A549 cells was abolished in SK-MES-1 cells that do not have wild type TP53 protein. An additive effect against cell proliferation by budesonide and fenofibrate combination was observed only in TP53 wild type A549 cancer cells. Analysis of cell cycle distribution and cyclin profile indicated that the inhibition of cell proliferation was associated with G1 cell cycle arrest. The suppression of NF-κB activity and ERK signaling may contribute to the inhibition of cell proliferation by budesonide and or fenofibrate. The additive inhibitory effect on cell proliferation by budesonide and fenofibrate combination suggests that the same or greater therapeutic effect could be achieved with reduced dosage and side effects when the two compounds are applied simultaneously.

KEYWORDS:

budesonide; fenofibrate; glucocorticoid receptor (GR); lung cancer; peroxisome proliferator-activated receptor α (PPARα)

PMID:
23625588
DOI:
10.1002/mc.22029
[Indexed for MEDLINE]
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