Chemoprevention of breast cancer by targeting cyclooxygenase-2 and peroxisome proliferator-activated receptor-γ (Review)
- Authors:
- Published online on: June 1, 2002 https://doi.org/10.3892/ijo.20.6.1109
- Pages: 1109-1122
Metrics: Total
Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Abstract
Cyclooxygenase-2 (COX-2) and peroxisome proliferator-activated receptor-γ (PPARγ) have emerged as candidate molecules that hold great promise for cancer chemoprevention. COX-2 increased expression and PPARγ inactivation occur during mammary gland carcinogenesis. COX-2 and PPARγ may contribute to breast cancer induction either directly or via their effects on factors known to influence tumor development, e.g., nuclear factor-κB and vascular endothelial growth factor. Inhibition of COX-2 or activation of PPARγ prevents mammary carcinomas in experimental animals with little toxicity. Combinational treatment with COX-2 inhibitor and PPARγ 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 PPARγ 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 PPARγ 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.