Signal transduction network leading to COX-2 induction: a road map in search of cancer chemopreventives.
Cancer is still a major global health concern even after an everlasting strive in conquering this dread disease. Emphasis is now given to chemoprevention to reduce the risk of cancer and also to improve the quality of life among cancer afflicted individuals. Recent progress in molecular biology of cancer has identified key components of the cellular signaling network, whose functional abnormality results in undesired alterations in cellular homeostasis, creating a cellular microenvironment that favors premalignant and malignant transformation. Multiple lines of evidence suggest an elevated expression of cyclooxygenase-2 (COX-2) is causally linked to cancer. In response to oxidative/pro-inflammatory stimuli, turning on unusual signaling arrays mediated through diverse classes of kinases and transcription factors results in aberrant expression of COX-2. Population-based as well as laboratory studies have explored a broad spectrum of chemopreventive agents including selective COX-2 inhibitors and a wide variety of anti-inflammatory phytochemicals, which have been shown to target cellular signaling molecules as underlying mechanisms of chemoprevention. Thus, unraveling signaling pathways regulating aberrant COX-2 expression and targeted blocking of one or more components of those signal cascades may be exploited in searching chemopreventive agents in the future.
Surh
Young-Joon
YJ
National Research Laboratory of Molecular Carcinogenesis and Chemoprevention, College of Pharmacy, Seoul National University, Seoul 151-742, Korea. surh@plaza.snu.ac.kr
Kundu
Joydeb Kumar
JK
D000818:Animals; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use*; D004790:Enzyme Induction / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008565:Membrane Proteins; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000517:prevention & control*; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology*
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D008565:Membrane Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases