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Maradeo Marie E , Eldeen Mazen B , Badawi Alaa F
Combinational chemoprevention of breast cancer by targeting cyclooxygenase-2 and peroxisome proliferator-activated receptor-g
Horizons in Cancer Research. 2006 ;36(New Breast Cancer Research) :95-109
PMID: AN 2006:667356
AbstractCyclooxygenase-2 (COX-2) and peroxisome proliferator-activated receptor-g (PPAR-g) have emerged as candidate mols. that hold a promise for the chemoprevention of breast cancer. Evidence suggests that upregulation of COX-2 expression and inactivation of PPAR-g may take place during the development and progression of breast cancer. Inhibition of COX-2 or activation of PPAR-g prevents mammary carcinomas in exptl. animals. It appears that COX-2 and PPAR-g may contribute to breast cancer induction either directly or via their affects on mol. pathways known to influence tumor development and progression, e.g., cell proliferation and apoptosis. Therefore, both mols. were thought to coordinately influence not only breast cancer development but also its progression to metastasis. Consequently, we hypothesized that simultaneous targeting of both mols. may provide an effective strategy to prevent breast cancer and that a combined treatment with COX-2 inhibitor and PPAR-g agonists may result in synergistic anti-tumorigenic effects with low toxicity. Establishing a relationship between COX-2 and PPAR-g in breast cancer should generate fundamental knowledge that will enhance our understanding of the mechanism(s) by which this tumor develops and progresses into metastasis, and can, consequently, provide the basis for a novel and effective strategy for breast cancer prevention. This article summarizes several of the recent studies developed in our lab. with a major goal to elucidate a detailed preclin. evaluation for targeting COX-2 and PPAR-g in the prevention of human breast cancer. In general, these studies include both human (tissues and cell lines) and animal models and provided evidence regarding the involvement of COX-2 and PPAR-g in human breast cancer and that simultaneous targeting of both mols. may be an effective approach for the prevention of this malignancy. [on SciFinder (R)]
Notes1 Pharmacology Division of Population Science,Fox Chase Cancer Center,Philadelphia,USA. Journal; General Review written in English.