Resveratrol directly targets COX-2 to inhibit carcinogenesis

Tatiana Zykova, Feng Zhu, Xiuhong Zhai, Wei-Ya Ma, Svetlana P. Ermakova, Won Lee Ki, Ann M. Bode, Zigang Dong

Research output: Contribution to journalArticlepeer-review

167 Scopus citations


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-frans-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-transstilbene (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.

Original languageEnglish (US)
Pages (from-to)797-805
Number of pages9
JournalMolecular Carcinogenesis
Issue number10
StatePublished - Oct 2008


  • Cell transformation
  • Fluorescence
  • Resveratrol analogs


Dive into the research topics of 'Resveratrol directly targets COX-2 to inhibit carcinogenesis'. Together they form a unique fingerprint.

Cite this