Allyl isothiocyanate (AITC) and phenyl isothiocyanate (PITC) inhibit tumour-specific angiogenesis by downregulating nitric oxide (NO) and tumour necrosis factor-alpha (TNF-alpha) production.

Abstract

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-alpha level during angiogenesis. In vivo antiangiogenic 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 microg/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-alpha production. These results clearly demonstrated that AITC and PITC inhibited tumour-specific angiogenesis by downregulating NO and TNF-alpha production.

• Authors: Punathil Thejass, Girija Kuttan
• Journal: Nitric oxide : biology and chemistry (Nitric Oxide) Vol. 16 Issue 2 Pg. 247-57 (Mar 2007) ISSN: 1089-8603 [Print] United States
• PMID: 17097904 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Isothiocyanates
• Tumor Necrosis Factor-alpha
• Nitric Oxide

Topics

• Animals
• Aorta (drug effects)
• Cell Line, Tumor
• Down-Regulation (drug effects)
• In Vitro Techniques
• Isothiocyanates (pharmacology)
• Macrophages (drug effects, metabolism)
• Male
• Melanoma, Experimental (blood supply)
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Neovascularization, Pathologic
• Nitric Oxide (biosynthesis)
• Rats
• Tumor Necrosis Factor-alpha (biosynthesis)