Sulforaphane suppresses angiogenesis and disrupts endothelial mitotic progression and microtubule polymerization

Steven J.T. Jackson, Keith W. Singletary, Richard C. Venema

Research output: Contribution to journalArticle

69 Citations (Scopus)

Abstract

Sulforaphane (SUL), an isothiocyanate derived from broccoli and other cruciferous vegetables, is known to induce phase II detoxification enzymes, disrupt cancer cell microtubule polymerization, and trigger cell cycle arrest in breast and colon cancer cells. Here, we provide the first evidence that SUL also acts to inhibit angiogenesis via suppression of endothelial cellproliferation. Bovine aortic endothelial (BAE) cells were exposed to concentrations of up to 15 μM SUL prior to cell cycle analysis and mitotic index quantification. Within 24 h, 15 μM SUL clearly induced G2/M accumulation and pre-metaphase arrest in BAE cells. Moreover, immunofluorescence tubulin staining indicated that this same SUL concentration was efficacious in not only disrupting mitotic progression, but also in perturbing normal polymerization of mitotic (and cytoplasmic) microtubules. Furthermore, daily administration of SUL (100 nmol/day, i.v. for 7 days) to female Balb/c mice bearing VEGF-impregnated Matrigel plugs strongly and significantly (P < 0.05) suppressed angiogenesis progression as measured by hemoglobin concentration. Taken together, these findings suggest that the endothelial cell population is a novel target of SUL action both in vitro and in vivo. This mechanism of SUL-induced endothelial microtubule disruption and early mitotic arrest may further discern a potential role of SUL as a chemopreventive agent.

Original languageEnglish (US)
Pages (from-to)77-84
Number of pages8
JournalVascular Pharmacology
Volume46
Issue number2
DOIs
StatePublished - Feb 1 2007

Fingerprint

Microtubules
Polymerization
Endothelial Cells
Phase II Metabolic Detoxication
sulforafan
Mitotic Index
Brassica
Tubulin
Metaphase
Cell Cycle Checkpoints
Vegetables
Colonic Neoplasms
Vascular Endothelial Growth Factor A
Fluorescent Antibody Technique
Cell Cycle
Hemoglobins
Staining and Labeling
Breast Neoplasms
Enzymes
Population

Keywords

  • Angiogenesis
  • Microtubules
  • Mitotic arrest
  • Sulforaphane

ASJC Scopus subject areas

  • Physiology
  • Molecular Medicine
  • Pharmacology

Cite this

Sulforaphane suppresses angiogenesis and disrupts endothelial mitotic progression and microtubule polymerization. / Jackson, Steven J.T.; Singletary, Keith W.; Venema, Richard C.

In: Vascular Pharmacology, Vol. 46, No. 2, 01.02.2007, p. 77-84.

Research output: Contribution to journalArticle

Jackson, Steven J.T. ; Singletary, Keith W. ; Venema, Richard C. / Sulforaphane suppresses angiogenesis and disrupts endothelial mitotic progression and microtubule polymerization. In: Vascular Pharmacology. 2007 ; Vol. 46, No. 2. pp. 77-84.
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