Sodium butyrate inhibits angiogenesis of human intestinal microvascular endothelial cells through COX-2 inhibition.
We examined the effect of sodium butyrate on in vitro angiogenesis and cyclooxygenase (COX) expression using primary cultures of human intestinal microvascular endothelial cells (HIMEC). Butyrate inhibited VEGF-induced cellular proliferation, transmigration and tube formation of HIMEC. Butyrate also inhibited COX-2 expression as well as prostaglandin (PG)E2 and PGI2 production, and administration of PGI2 analog partially reversed the effect of butyrate on HIMEC angiogenesis. These results indicate that sodium butyrate inhibits HIMEC angiogenesis through down-regulation of COX-2 expression and PG production, and suggest that anti-angiogenic mechanisms may also be involved in the inhibitory effect of sodium butyrate on tumor growth.
Department of Medicine, Division of Gastroenterology and Hepatology, Digestive Disease Center, Froedtert Memorial Lutheran Hospital, Milwaukee Veterans Administration Medical Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Hitoshi
H
Ogawa
Parvaneh
P
Rafiee
Pamela J
PJ
Fisher
Nathan A
NA
Johnson
Mary F
MF
Otterson
David G
DG
Binion
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D002087:Butyrates / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000096:biosynthesis; D004336:Drug Antagonism; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects; D011464:Epoprostenol / Q000096:biosynthesis; D006801:Humans; D007422:Intestines / Q000098:blood supply*; D007527:Isoenzymes / Q000096:biosynthesis / Q000502:physiology; D008565:Membrane Proteins; D008833:Microcirculation; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology
D020533:Angiogenesis Inhibitors; D002087:Butyrates; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D042461:Vascular Endothelial Growth Factor A; D011464:Epoprostenol; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone