Cancer preventive phytochemicals as speed breakers in inflammatory signaling involved in aberrant COX-2 expression

Abstract

A causal association between inflammation and cancer has long been suspected. Multiple lines of compelling evidence from clinical, epiderniologic and laboratory studies support that inflammation plays a critical role in the promotion and progression stages of carcinogenesis. Recent progress in our understanding of the molecular biology of cancer highlights the intracellular signal transduction network, including-that involved in mediating the inflammatory response, which often functions abnormally during carcinogenesis. One of the key players in inflammatory signaling is cyclooxygenase-2 (COX-2). Aberrant upregulation of COX-2 is frequently observed in various precancerous and malignant tissues. Pro-inflammatory stimuli trigger the activation of an intracellular signal transduction network comprising proline-directed serine/threonine kinases, and their downstream transcription factors, resulting in an inappropriate induction of COX-2. Therefore, the normalization of inappropriately overamplified signaling cascades implicated in chronic inflammation-associated carcinogenesis by use of COX-2 specific inhibitors has been recognized as a rational and pragmatic strategy in molecular target-based cancer prevention. This review highlights the cancer preventive effects of some anti- in flammato ry phytochemicals derived from edible plants, and their underlying molecular mechanisms with a focus on representative transcription factors and upstream kinases responsible for COX-2 induction.