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Diallyl trisulfide inhibits angiogenic features of human umbilical vein endothelial cells by causing Akt inactivation and down-regulation of VEGF and VEGF-R2.

Diallyl trisulfide inhibits angiogenic features of human umbilical vein endothelial cells by causing Akt inactivation and down-regulation of VEGF and VEGF-R2. Research Abstract Details 

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  • Diallyl trisulfide inhibits angiogenic features of human umbilical vein endothelial cells by causing Akt inactivation and down-regulation of VEGF and VEGF-R2. Abstract Text:

    dong xiaoDong Xiao,mengfeng liMengfeng Li,anna herman-antosiewiczAnna Herman-Antosiewicz,jedrzej antosiewiczJedrzej Antosiewicz,hui xiaoHui Xiao,karen l lewKaren L Lew,yan zengYan Zeng,stanley w marynowskiStanley W Marynowski,shivendra v singhShivendra V Singh,

    We have shown recently that diallyl trisulfide (DATS), a cancer-chemopreventive constituent of garlic, inactivates Akt to trigger mitochondrial translocation of proapoptotic protein BAD in human prostate cancer cells. Because Akt activation is implicated in the promotion of endothelial cell survival and angiogenesis, we hypothesized that DATS may inhibit angiogenesis. In the present study, we tested this hypothesis using human umbilical vein endothelial cells (HUVECs) as a model. Survival of HUVECs was reduced significantly in the presence of DATS in a concentration-dependent manner, with an IC50 of approximately 4 microM. The DATS-mediated suppression of HUVEC survival was associated with apoptosis induction characterized by accumulation of subdiploid cells, cytoplasmic histone-associated DNA fragmentation, and cleavage of caspase-3 and poly-(ADP-ribose)-polymerase. The DATS-induced DNA fragmentation was significantly attenuated in the presence of pan-caspase inhibitor zVAD-fmk and specific inhibitors of caspase-9 (zLEHD-fmk) and caspase-8 (zIETD-fmk). DATS treatment inhibited the formation of capillary-like tube structure and migration by HUVECs in association with suppression of vascular endothelial growth factor (VEGF) secretion and VEGF receptor-2 protein level and inactivation of Akt kinase. DATS treatment also caused activation of extracellular signal-regulated kinase 1/2 (ERK1/2) but not c-Jun NH2-terminal kinase (JNK) or p38 mitogen-activated protein kinase (p38MAPK).DATS-mediatedapoptosis induction and inhibition of HUVEC tube formation was partially but statistically significantly attenuated by pharmacologic inhibition of ERK1/2 but not JNK or p38MAPK. The present study demonstrates, for the first time, that DATS has the ability to inhibit angiogenic features of human endothelial cells.

    Diallyl trisulfide inhibits angiogenic features of human umbilical vein endothelial cells by causing Akt inactivation and down-regulation of VEGF and VEGF-R2. Publishing Authors By Initials

    d xiaoD Xiao,m liM Li,a herman-antosiewiczA Herman-Antosiewicz,j antosiewiczJ Antosiewicz,h xiaoH Xiao,kl lewKL Lew,y zengY Zeng,sw marynowskiSW Marynowski,sv singhSV Singh,

    For similar abstracts research abstracts see: abstracts research

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    Diallyl trisulfide inhibits angiogenic features of human umbilical vein endothelial cells by causing Akt inactivation and down-regulation of VEGF and VEGF-R2. Journal Published:

    PUBLICATION TYPE: Research Support, Non-U.S. Gov

    Journal: Nutrition and cancer

    VOLUME: 55

    Page Numbers: 94-107

    Journal Abbreviation:

    ISSN: 0163-5581

    DAY: 3

    MONTH: 12

    YEAR: 2006

    Diallyl trisulfide inhibits angiogenic features of human umbilical vein endothelial cells by causing Akt inactivation and down-regulation of VEGF and VEGF-R2. Information

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    LANGUAGE: eng

    NlmUniqueID: 7905040

    Diallyl trisulfide inhibits angiogenic features of human umbilical vein endothelial cells by causing Akt inactivation and down-regulation of VEGF and VEGF-R2. Keywords Mesh Terms:

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    Grant and Affiliation Information for Diallyl trisulfide inhibits angiogenic features of human umbilical vein endothelial cells by causing Akt inactivation and down-regulation of VEGF and VEGF-R2.

    AFFILIATION: University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.

    Country: United States

    United States Research PublicationUnited States Research Publication

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    MEDLINETA: Nutr Cancer

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