Quercetin inhibits eNOS, microtubule polymerization, and mitotic progression in bovine aortic endothelial cells

Steven J T Jackson, Richard C. Venema

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

Quercetin (QRN), one of the most abundant flavonoids in the human diet, is a known antioxidant and inhibitor of cancer cell cycle progression. Here, we provide the first evidence that QRN inhibits angiogenesis via a mechanism involving both suppression of endothelial nitric oxide synthase (eNOS) and early M-phase cell cycle arrest. Bovine aortic endothelial (BAE) cells were exposed to doses of up to 100 μmol/L QRN and assayed for eNOS activity and phosphorylation status. Phosphorylation of eNOS at Ser 617 (bovine sequence) is thought to occur in response to Akt stimulation and to be required for eNOS activity. Together with basal eNOS activity, eNOS phosphorylation at Ser 617 and Akt Ser 473 phosphorylation were dose dependently and concomitantly suppressed by QRN within 30 min. Furthermore, although the significant (P < 0.05) inhibitory effect of a single 100 μmol/L QRN dose on eNOS activity was overcome within ∼24 h, chronic QRN exposures (24-48 h) led to early M-phase arrest and disruption of mitotic microtubule polymerization. In vivo, QRN administered i.p. to female Balb/C mice bearing both syngeneic mammary tumors and Matrigel implants suppressed angiogenesis as measured by endothelial cell immunohistochemistry and hemoglobin concentration. Taken together, these findings suggest a dual mechanism by which QRN suppresses endothelial cell proliferation, both acutely via inhibition of eNOS Ser 617 phosphorylation, and chronically via perturbation of mitotic microtubule polymerization. This novel mechanism of QRN in endothelial cells may in part explain its inhibitory action on angiogenesis and further discern a potential role of QRN as a chemopreventive agent.

Original languageEnglish (US)
Pages (from-to)1178-1184
Number of pages7
JournalJournal of Nutrition
Volume136
Issue number5
StatePublished - May 1 2006

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Nitric Oxide Synthase Type III
Quercetin
Microtubules
Polymerization
polymerization
quercetin
microtubules
endothelial cells
Endothelial Cells
cattle
phosphorylation
Phosphorylation
angiogenesis
mitosis
dosage
endothelial nitric oxide synthase
M Phase Cell Cycle Checkpoints
mammary neoplasms (animal)
Flavonoids
Cell Division

Keywords

  • eNOS phosphorylation
  • Microtubules
  • Mitotic arrest
  • Quercetin

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Food Science

Cite this

Quercetin inhibits eNOS, microtubule polymerization, and mitotic progression in bovine aortic endothelial cells. / Jackson, Steven J T; Venema, Richard C.

In: Journal of Nutrition, Vol. 136, No. 5, 01.05.2006, p. 1178-1184.

Research output: Contribution to journalArticle

Jackson, Steven J T ; Venema, Richard C. / Quercetin inhibits eNOS, microtubule polymerization, and mitotic progression in bovine aortic endothelial cells. In: Journal of Nutrition. 2006 ; Vol. 136, No. 5. pp. 1178-1184.
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