Inhibition of phorbol ester-induced COX-2 expression by some edible African plants.
Cancer bush (CB, Sutherlandia frutescens), Devil's claw (DEV, Harpagophytum procumbens), Rooibos tea (RT, Aspalathus linearis), and Bambara groundnut (BB, Vignea subterranean) have been used to treat some malignancies and inflammatory disorders in Africa. However, biochemical basis for chemopreventive effects of these medicinal plants remains unclear. An abnormally elevated expression of cyclooxygenase-2 (COX-2) has been implicated in pathogenesis and progression of carcinogenesis. In the present study, we found that the methanol extracts of CB, DEV, RT, and BB inhibited, to a different extent, 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced COX-2 expression in human breast epithelial (MCF10A) cells and in mouse skin in vivo. To determine the molecular mechanism of COX-2 inhibition by the above medicinal plants, we examined their effects on activation of NF-kappaB which is one of the major transcription factors responsible for regulating COX-2 expression. Methanol extracts of both CB and BB inhibited the DNA binding of NF-kappaB activated by TPA in MCF10A cells in a dose-dependent manner. Based on above findings, CB and BB are likely to inhibit TPA-induced COX-2 expression through suppression of DNA binding of NF-kappaB, which may contribute to the chemopreventive or chemoprotective activity of these African plants.
Na
Hye-Kyung
HK
Laboratory of Biochemistry and Molecular Toxicology, College of Pharmacy, Seoul National University, South Korea.
Mossanda
Kensese S
KS
Lee
Ji-Yoon
JY
Surh
Young-Joon
YJ
D000349:Africa; D000818:Animals; D010367:Arachis; D001940:Breast; D002460:Cell Line; D051546:Cyclooxygenase 2; D004847:Epithelial Cells; D005260:Female; D006801:Humans; D008565:Membrane Proteins; D051379:Mice; D008813:Mice, Inbred ICR; D016328:NF-kappa B / Q000378:metabolism; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology*; D010945:Plants, Edible / Q000502:physiology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects / Q000235:genetics*; D013662:Tea; D013755:Tetradecanoylphorbol Acetate / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D008565:Membrane Proteins; D016328:NF-kappa B; D010936:Plant Extracts; D013662:Tea; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D013755:Tetradecanoylphorbol Acetate