Suppressive effect and mechanism of saxatilin, a disintegrin from Korean snake (Gloydius saxatilis), in vascular smooth muscle cells

Sohn, Young-Doug; Cho, Kil-Sang; Sun, Sae-Ah; Sung, Hee-Jin; Kwak, Kyu-Won; Hong, Seunghun; Kim, Doo-Sik; Chung, Koo–Hyun

doi:10.1016/j.toxicon.2008.06.020

Cited by 8 publications

(5 citation statements)

References 15 publications

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“…Indeed, Echistatin, a snake ( Echis carinatus ) venom disintegrin targeting αvβ3, did not activate ERK 1/2 in this cell line . However, Saxatilin (a disintegrin from a Gloydius saxatilis snake venom, that interacts with αIIbβ3 and αvβ3 integrins), suppressed the growth factor‐induced proliferation of human coronary artery smooth muscle cells (HCASMCs) through the activation of ERKs, increased levels of CDK inhibitors p21 and p27, and the reduced cyclin D1/2 and E expression levels . Moreover, ERK 1/2 activation correlated with cell death induced by anti‐tumor compounds, such as resveratrol , betulinic acid or taxol .…”

Section: Discussionmentioning

confidence: 96%

Lebein, a snake venom disintegrin, suppresses human colon cancer cells proliferation and tumor-induced angiogenesis through cell cycle arrest, apoptosis induction and inhibition of VEGF expression

et al. 2016

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Lebein, is an heterodimeric disintegrin isolated from Macrovipera lebetina snake venom that was previously characterized as an inhibitor of ADP-induced platelet aggregation. In this study, we investigated the effect of Lebein on the p53-dependent growth of human colon adenocarcinoma cell lines. We found that Lebein significantly inhibited LS174 (p53wt), HCT116 (p53wt), and HT29 (p53mut) colon cancer cell viability by inducing cell cycle arrest through the modulation of expression levels of the tumor suppression factor p53, cell cycle regulating proteins cyclin D1, CDK2, CDK4, retinoblastoma (Rb), CDK1, and cyclin-dependent kinase inhibitors p21 and p27. Interestingly, Lebein-induced apoptosis of colon cancer cells was dependent on their p53 status. Thus, in LS174 cells, cell death was associated with PARP cleavage and the activation of caspases 3 and 8 while in HCT116 cells, Lebein induced caspase-independent apoptosis through increased expression of apoptosis inducing factor (AIF). In LS174 cells, Lebein triggers the activation of the MAPK ERK1/2 pathway through induction of reactive oxygen species (ROS). It also decreased cell adhesion and migration to fibronectin through down regulation of α5β1 integrin. Moreover, Lebein significantly reduced the expression of two angiogenesis stimulators, Vascular Endothelial Growth Factor (VEGF) and Neuropilin 1 (NRP1). It inhibited the VEGF-induced neovascularization process in the quail embryonic CAM system and blocked the development of human colon adenocarcinoma in nude mice. Overall, our work indicates that Lebein may be useful to design a new therapy against colon cancer. © 2016 Wiley Periodicals, Inc.

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Section: Discussionmentioning

confidence: 96%

Lebein, a snake venom disintegrin, suppresses human colon cancer cells proliferation and tumor-induced angiogenesis through cell cycle arrest, apoptosis induction and inhibition of VEGF expression

et al. 2016

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“…Eristostatin treatment did not prevent tumor cell extravasation or migration [60]. However, it was shown later that eristostatin inhibited melanoma cell motility, an effect mediated by fibronectin-binding integrins [61].…”

Section: Proteinsmentioning

confidence: 95%

Snake Venom Peptides: Promising Molecules with Anti-Tumor Effects

Sarray¹,

Luis²,

Ayeb³

et al. 2013

Bioactive Food Peptides in Health and Disease

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“…A monomeric recombinant RGD-disintegrin from Bothrops alternatus venom, Dis Ba -01, produces similar effects in the matrigel plug model in nude mice [33]. In addition to inhibition of EC migration, saxatilin, an RGD disintegrin from Gloydius saxatilis also inhibited the migration of vitronectin-induced smooth muscle cells [54,55]. …”

Section: Effects Of Disintegrins On Endothelial Cell Migration Andmentioning

confidence: 99%

“…Morris et al [64], were one of the first investigators to test eristostatin, an RGD-disintegrin from Eristocophis macmahoni , on individual metastasis steps such as cell arrest, extravasation and migration. Eristostatin treatment did not prevent tumor cell extravasation or migration [55]. However, it was shown later that eristostatin inhibited melanoma cell motility, an effect mediated by fibronectin-binding integrins [56].…”

Section: Effects Of Disintegrins On Tumor Cell Migrationmentioning

confidence: 99%

Snake Venom Disintegrins and Cell Migration

Selistre-de-Araújo

Pontes

Montenegro

et al. 2010

Toxins

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Cell migration is a key process for the defense of pluricellular organisms against pathogens, and it involves a set of surface receptors acting in an ordered fashion to contribute directionality to the movement. Among these receptors are the integrins, which connect the cell cytoskeleton to the extracellular matrix components, thus playing a central role in cell migration. Integrin clustering at focal adhesions drives actin polymerization along the cell leading edge, resulting in polarity of cell movement. Therefore, small integrin-binding proteins such as the snake venom disintegrins that inhibit integrin-mediated cell adhesion are expected to inhibit cell migration. Here we review the current knowledge on disintegrin and disintegrin-like protein effects on cell migration and their potential use as pharmacological tools in anti-inflammatory therapy as well as in inhibition of metastatic invasion.

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Suppressive effect and mechanism of saxatilin, a disintegrin from Korean snake (Gloydius saxatilis), in vascular smooth muscle cells

Cited by 8 publications

References 15 publications

Lebein, a snake venom disintegrin, suppresses human colon cancer cells proliferation and tumor-induced angiogenesis through cell cycle arrest, apoptosis induction and inhibition of VEGF expression

Lebein, a snake venom disintegrin, suppresses human colon cancer cells proliferation and tumor-induced angiogenesis through cell cycle arrest, apoptosis induction and inhibition of VEGF expression

Snake Venom Peptides: Promising Molecules with Anti-Tumor Effects

Snake Venom Disintegrins and Cell Migration

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