#C174 Antiangiogenic Properties of Sulforaphane, an Isothiocyanate Derived from Broccoli. Lisa Bertl, Helmut Bartsch, Clarissa Gerhauser, German Cancer Research Center (DKFZ), Heidelberg, Germany. Angiogenesis - the formation of new blood vessels from already established microvasculature - plays a pivotal role in the growth of solid tumors and the spreading of metastases. Therefore, inhibition of angiogenesis provides an alternative additional approach to chemoprevention. Sulforaphane (SFN) is an aliphatic isothiocyanate found as a precursor glucosinolate in cruciferous vegetables like broccoli. Its chemopreventive activity, demonstrated by inhibition of chemically-induced rat mammary carcinogenesis and prevention of aberrant crypt foci in rat colon, has mainly been attributed to the modulation of carcinogen metabolism by inhibition of Phase 1 and induction of Phase 2 enzymes. Recently, we could demonstrate that SFN exerts anti-inflammatory activity, including inhibition of iNOS, Cox-2 and TNF-á induction, by thiol-dependent inhibition of NF-êB DNA binding (Heiss et al., JBC 276, 32008, 2001). To investigate the effect of SFN on angiogenesis, we established a human in vitro anti-angiogenic assay premised on the principle of wound healing. Using this model, SFN was identified as a novel potent inhibitor of angiogenesis. We observed a dose-dependent growth reduction of newly formed capillaries in a concentration range of 0.01 − 20 ìM, with an IC50 of 0.08 ìM. Resveratrol used as a positive control substance was 41% inhibitory at a 1 ìM concentration. Further mechanistic investigations were performed with HMEC-1, an immortalized human microvascular endothelial cell line. SFN potently inhibited tube-formation on basement membrane matrix at 10 and 1 ìM, respectively, whereas at 0.1 ìM, some tubes started to form within the incubation period of 6 h. Also, SFN effectively inhibited migration of HMEC-1 cells after wounding in a wound closure assay (95% inhibition at 10 ìM, IC50 = 0.63 ìM). These effects were only partly due to inhibition of HMEC-1 proliferation as SFN inhibited cell growth by 42% at 10 ìM, with an IC50 of 11.3 ìM. To elucidate the effects of SFN on molecular signaling pathways leading to angiogenesis, we utilized cultured 264.7 Raw macrophages. Stimulation with lipopolysaccharide (LPS) or 12-O-tetradecanoylphorbol-13-acetate leads to an upregulation of pro-angiogenic factors including vascular endothelial growth factor (VEGF), nitric oxide, tumor necrosis factor á, prostaglandins, polyamines and the proto-oncogene c-Myc, a master regulator of angiogenesis. By RT-PCR we could show that SFN reduced LPS-induced mRNA expression of VEGF, iNOS, Cox-2 and c-Myc in a time- and dose-dependent manner. Since all these genes are regulated by NF-êB, inhibition of its DNA binding by SFN might play a key role in the observed suppression of angiogenesis. Frontiers in Cancer Prevention Research, 2003 AACR Remember we are NOT Doctors and have NO medical training. This site is like an Encylopedia - there are many pages, many links on many topics. Support our work with any size DONATION - see left side of any page - for how to donate. You can help raise awareness of CAM.