Suppression by flavonoids of cyclooxygenase-2 promoter-dependent transcriptional activity in colon cancer cells: structure-activity relationship.

Abstract

Cyclooxygenase-2 (COX-2) plays an important role in carcinogenesis. Investigation of the suppressive action of twelve flavonoids of different chemical classes on the transcriptional activity of the COX-2 gene in human colon cancer DLD-1 cells using a reporter gene assay have revealed quercetin to be the most potent suppressor of COX-2 transcription (IC50 = 10.5 microM), while catechin and epicatechin showed weak activity (IC50 = 415.3 microM). Flavonoids have three heterocyclic rings as a common structure. A structure-activity study indicated that the number of hydroxyl groups on the B ring and an oxo group at the 4-position of the C ring are important in the suppression of COX-2 transcriptional activity. A low electron density of the oxygen atom in the hydroxyl group of the A ring was also important. Further examination of the role of the hydroxyl group in the A ring showed that bromination of resacetophenone to give 3,5-dibromo-2,4-dihydroxyacetophenone resulted in a 6.8-fold increase in potency for suppressing COX-2 promoter activity. These results provide a basis for the design of improved suppressors of COX-2 transcriptional activity.

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@article{Mutoh2000SuppressionBF, title={Suppression by flavonoids of cyclooxygenase-2 promoter-dependent transcriptional activity in colon cancer cells: structure-activity relationship.}, author={Masato Mutoh and Megumi Takahashi and Kazuhiko Fukuda and Haruki Komatsu and Takeshi Enya and Yuko Matsushima-Hibiya and Hiroyuki Mutoh and Takashi Sugimura and Keiji Wakabayashi}, journal={Japanese journal of cancer research : Gann}, year={2000}, volume={91 7}, pages={686-91} }