期刊
NITRIC OXIDE-BIOLOGY AND CHEMISTRY
卷 16, 期 2, 页码 247-257出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.niox.2006.09.006
关键词
allyl isothiocyanate; angiogenesis; macrophage; nitric oxide; phenyl isothiocyanate; tumour necrosis factor-alpha
Angiogenesis, a crucial step in the growth and metastasis of cancers, is initiated with vasodilation mediated by nitric oxide (NO). The pro-inflammatory cytokine, tumour necrosis factor-alpha (TNF-alpha), is a mediator of nitric oxide synthesis. We analyzed the effect of allyl isothiocyanate (AITC) and phenyl isothiocyanate (PITC) on serum NO as well as TNF-a level during angiogenesis. In vivo anti-angiogenic activity was studied using B16F-10 melanoma cell-induced capillary formation in C57BL/6 mice. Intraperitoneal administration of AITC and PITC at a concentration of 25 mu g/dose/animal significantly inhibited tumour-directed capillary formation. Treatment of AITC and PITC significantly downregulated serum NO as well as TNF-alpha level in angiogenesis-induced animals compared to untreated control animals. The in vitro antiangiogenic study, using rat aortic ring assay, showed that both AITC and PITC at non-toxic concentrations inhibited the production of proangiogenic factors from B16F-10 melanoma cells which was evident with the inhibition of microvessel outgrowth from aortic rings. Both AITC and PITC significantly inhibited sodium nitroprusside as well as TNF-alpha-induced microvessel outgrowth from rat aortic ring. Administration of AITC and PITC also significantly reduced NO and TNF-alpha production by LPS-stimulated macrophages both in vivo as well as in vitro. Bio-assay using serum of angiogenesis-induced animals and supernatant from LPS-stimulated macrophages clearly confirmed the downregulatory action of AITC and PITC on TNF-a production. These results clearly demonstrated that AITC and PITC inhibited tumour-specific angiogenesis by downregulating NO and TNF-alpha production. (c) 2006 Elsevier Inc. All rights reserved.
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