Resveratrol directly targets COX‐2 to inhibit carcinogenesis
- 31 March 2008
- journal article
- research article
- Published by Wiley in Molecular Carcinogenesis
- Vol. 47 (10) , 797-805
- https://doi.org/10.1002/mc.20437
Abstract
Targeted molecular cancer therapies can potentially deliver treatment directly to a specific protein or gene to optimize efficacy and reduce adverse side effects often associated with traditional chemotherapy. Key oncoprotein and oncogene targets are rapidly being identified based on their expression, pathogenesis and clinical outcome. One such protein target is cyclooxygenase‐2 (COX‐2), which is highly expressed in various cancers. Research findings suggest that resveratrol (RSVL; 3,5,4′‐trihydroxy‐trans‐stilbene) demonstrates nonselective COX‐2 inhibition. We report herein that RSVL directly binds with COX‐2 and this binding is absolutely required for RSVL's inhibition of the ability of human colon adenocarcinoma HT‐29 cells to form colonies in soft agar. Binding of COX‐2 with RSVL was compared with two RSVL analogues, 3,3′,4′,5′,5‐pentahydroxy‐trans‐stilbene (RSVL‐2) or 3,4′,5‐trimethoxy‐trans‐stilbene (RSVL‐3). The results indicated that COX‐2 binds with RSVL‐2 more strongly than with RSVL, but does not bind with RSVL‐3. RSVL or RSVL‐2, but not RSVL‐3, inhibited COX‐2‐mediated PGE2 production in vitro and ex vivo. HT‐29 human colon adenocarcinoma cells express high levels of COX‐2 and either RSVL or RSVL‐2, but not RSVL‐3, suppressed anchorage independent growth of these cells in soft agar. RSVL or RSVL‐2 (not RSVL‐3) suppressed growth of COX‐2+/+ cells by 60% or 80%, respectively. Notably, cells deficient in COX‐2 were unresponsive to RSVL or RSVL‐2. These data suggest that the anticancer effects of RSVL or RSLV‐2 might be mediated directly through COX‐2.Keywords
This publication has 38 references indexed in Scilit:
- Resveratrol: A review of preclinical studies for human cancer preventionToxicology and Applied Pharmacology, 2007
- Resveratrol-induced cyclooxygenase-2 facilitates p53-dependent apoptosis in human breast cancer cellsMolecular Cancer Therapeutics, 2006
- COX-2: A Molecular Target for Colorectal Cancer PreventionJournal of Clinical Oncology, 2005
- Antiangiogenic properties of natural polyphenols from red wine and green teaThe Journal of Nutritional Biochemistry, 2004
- Targeting signal transduction pathways by chemopreventive agentsMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis, 2004
- Detection of an Intermediate during Unfolding of Bacterial Cell Division Protein FtsZJournal of Biological Chemistry, 2003
- Involvement of c‐jun NH2‐terminal kinases in resveratrol‐induced activation of p53 and apoptosisMolecular Carcinogenesis, 2002
- Cancer Chemopreventive Activity of Resveratrol, a Natural Product Derived from GrapesScience, 1997
- A Rapid and Sensitive Method for the Quantitation of Microgram Quantities of Protein Utilizing the Principle of Protein-Dye BindingAnalytical Biochemistry, 1976
- A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye bindingAnalytical Biochemistry, 1976