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Int J Oncol. 2002 Jun;20(6):1109-22.

Chemoprevention of breast cancer by targeting cyclooxygenase-2 and peroxisome proliferator-activated receptor-gamma (Review).

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  • 1Division of Population Science, Fox Chase Cancer Center, Philadelphia, PA 19111, USA. af_badawi@fccc.edu

Abstract

Cyclooxygenase-2 (COX-2) and peroxisome proliferator-activated receptor-gamma (PPARgamma) have emerged as candidate molecules that hold great promise for cancer chemoprevention. COX-2 increased expression and PPARgamma inactivation occur during mammary gland carcinogenesis. COX-2 and PPARgamma may contribute to breast cancer induction either directly or via their effects on factors known to influence tumor development, e.g., nuclear factor-kappaB and vascular endothelial growth factor. Inhibition of COX-2 or activation of PPARgamma prevents mammary carcinomas in experimental animals with little toxicity. Combinational treatment with COX-2 inhibitor and PPARgamma agonists may produce synergistic anti-tumorigenic effects without significant toxicity and, therefore, be an effective strategy to prevent human breast cancer. Establishing a relationship between COX-2 and PPARgamma in this malignancy may provide the basis for a novel chemopreventive strategy based on the modulation of both molecules simultaneously. This review evaluates experimental and epidemiological findings suggesting a possible role of COX-2 and PPARgamma in the development of human breast cancer and presents evidence substantiating their coordinated action in carcinogenesis and finally develops a rationale for the simultaneous targeting of both molecules as a potentially effective strategy to prevent breast malignancy.

PMID:
12011987
[PubMed - indexed for MEDLINE]
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