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Anti-Cancer Agents in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

Mechanisms Leading to COX-2 Expression and COX-2 Induced Tumorigenesis: Topical Therapeutic Strategies Targeting COX-2 Expression and Activity

Author(s): Aurelie Telliez, Christophe Furman, Nicole Pommery and Jean-Pierre Henichart

Volume 6, Issue 3, 2006

Page: [187 - 208] Pages: 22

DOI: 10.2174/187152006776930891

Price: $65

Abstract

The biological role of COX-2, the inducible form of cyclooxygenase, is to convert arachidonic acid into prostaglandins (PGs) and thromboxanes (TXs). Overexpressed in many tumors, COX-2 plays a crucial role in cancer through synthesis of PGs which stimulate PGs receptors with subsequent enhancement of cellular proliferation, promotion of angiogenesis, inhibition of apoptosis, stimulation of invasion/motility, and suppression of immune responses. Depending on the tissue specificity and the cell type, several signaling pathways (Kinases, Rho, cGMP and Wnt), and transcription factors such as AP1, NFAT or NF-kB, are involved in COX-2 expression. In this review, we will describe mechanisms required by COX-2 metabolites to promote cancer development, and also the signaling pathways leading to COX-2 expression. In order to counteract the negative effects of COX-2 in cancerogenesis, chemicals interfering with COX-2 activity and expression were designed. We will give in the last part of this article, an overview of these potent chemicals interfering with the COX-2 signaling pathways involved in its expression or with its activity.

Keywords: Cyclooxygenase-2, cancer, signaling pathways, therapeutic strategy


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