Chemoprevention of breast cancer by targeting cyclooxygenase-2 and peroxisome proliferator-activated receptor-gamma (Review).
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.
Badawi
Alaa F
AF
Division of Population Science, Fox Chase Cancer Center, Philadelphia, PA 19111, USA. af_badawi@fccc.edu
Badr
Mostafa Z
MZ
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000201:enzymology / Q000517:prevention & control*; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors* / Q000502:physiology; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology; D011453:Prostaglandins / Q000502:physiology; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists* / Q000502:physiology; D014157:Transcription Factors / Q000819:agonists* / Q000502:physiology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D011453:Prostaglandins; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases