Sulforaphane suppresses angiogenesis and disrupts endothelial mitotic progression and microtubule polymerization.
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 cell proliferation. Bovine aortic endothelial (BAE) cells were exposed to concentrations of up to 15 microM SUL prior to cell cycle analysis and mitotic index quantification. Within 24 h, 15 microM SUL clearly induced G(2)/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.
Jackson
Steven J T
SJ
Medical College of Georgia, Vascular Biology Center, CB 3330, 1459 Laney Walker Boulevard Augusta, GA 30912, USA.
Singletary
Keith W
KW
Venema
Richard C
RC
D020533:Angiogenesis Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology; D002417:Cattle; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D007279:Injections, Subcutaneous; D017879:Isothiocyanates; D007797:Laminin / Q000008:administration & dosage; D051379:Mice; D008807:Mice, Inbred BALB C; D008870:Microtubules / Q000187:drug effects* / Q000378:metabolism; D008938:Mitosis / Q000187:drug effects*; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D011509:Proteoglycans / Q000008:administration & dosage; D008941:Spindle Apparatus / Q000187:drug effects* / Q000378:metabolism; D040521:Subcutaneous Tissue / Q000098:blood supply; D013454:Sulfoxides; D013861:Thiocyanates / Q000494:pharmacology* / Q000627:therapeutic use; D013997:Time Factors; D050257:Tubulin Modulators / Q000494:pharmacology* / Q000627:therapeutic use; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage
D020533:Angiogenesis Inhibitors; D016588:Anticarcinogenic Agents; D004338:Drug Combinations; D017879:Isothiocyanates; D007797:Laminin; D011509:Proteoglycans; D013454:Sulfoxides; D013861:Thiocyanates; D050257:Tubulin Modulators; D042461:Vascular Endothelial Growth Factor A; C059485:matrigel; D003094:Collagen; C016766:sulforaphane