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Abstract:

Angiogenesis plays a critical role in initiating and promoting several diseases, such as cancer and herpetic stromal keratitis (HSK). Herein, we studied the inhibitory effect of two synthetic stigmasterol derivatives on capillary tube-like structures and on cell migration in human umbilical vein endothelial cells (HUVEC): (22S,23S)-22,23-dihydroxystigmast-4-en-3-one (compound 1) and (22S,23S)-3β-bromo-5α,22,23-trihydroxystigmastan-6-one (compound 2). We also studied their effect on VEGF expression in IL-6 stimulated macrophages and in LMM3 breast cancer cells. Furthermore, we investigated the antiangiogenic activity of the compounds on corneal neovascularization in the murine model of HSK and in an experimental model of tumor-induced angiogenesis in mice. Both compounds inhibited capillary tube-like formation, but only compound 1 restrained cell migration. Compound 1, unlike compound 2, was able to reduce VEGF expression. Only compound 1 not only reduced the incidence and severity of corneal neovascularization, when administered at the onset of HSK, but it also restrained the development of neovascular response induced by tumor cells in mice skin. Our results show that compound 1 inhibits angiogenesis in vitro and in vivo. Therefore, compound 1 would be a promising drug in the treatment of those diseases where angiogenesis represents one of the main pathogenic events. © 2016 Elsevier Inc.

Registro:

Documento: Artículo
Título:Synthetic stigmasterol derivatives inhibit capillary tube formation, herpetic corneal neovascularization and tumor induced angiogenesis: Antiangiogenic stigmasterol derivatives
Autor:Michelini, F.M.; Lombardi, M.G.; Bueno, C.A.; Berra, A.; Sales, M.E.; Alché, L.E.
Filiación:Universidad de Buenos Aires, Facultad de Ciencias Exactas y Naturales, Departamento de Química Biológica, Laboratorio de Virología, Consejo Nacional de Investigaciones Científicas y Técnicas, Instituto de Química Biológica de Facultad de Ciencias Exactas y Naturales (IQUIBICEN), Pabellón 2, 4to. piso, Ciudad Universitaria, C1428EGA Buenos Aires, Argentina
Universidad de Buenos Aires, Facultad de Medicina, Segunda Cátedra de Farmacología, Consejo Nacional de Investigaciones Científicas y Técnicas, Centro de Estudios Farmacológicos y Botánicos (CEFYBO), Paraguay 2155 Piso 16°, C1121ABG Buenos Aires, Argentina
Universidad de Buenos Aires, Facultad de Medicina, Departamento de Patología, Laboratorio de Investigaciones Oculares, J. E. Uriburu 950, EP, C1114AAD Buenos Aires, Argentina
Palabras clave:Antiangiogenic activity; Herpetic keratitis; HUVEC; Neovascularization; Stigmasterol derivative; Tumor; VEGF; 22,23 dihydroxystigmast 4 en 3 one; 3beta, bromo 5alpha,22,23 trihydroxystigmastan 6 one; interleukin 6; stigmasterol; unclassified drug; vasculotropin; stigmasterol; animal cell; animal experiment; animal model; antiangiogenic activity; Article; breast cancer cell line; capillary endothelial cell; cell invasion; controlled study; cornea neovascularization; female; herpes simplex keratitis; herpetic stromal keratitis; herpetic stromal keratitis; human; human cell; in vitro study; in vivo study; macrophage; male; migration inhibition; mouse; nonhuman; protein expression; topical treatment; umbilical vein endothelial cell; animal; Bagg albino mouse; cell line; cell survival; chemistry; Corneal Neovascularization; drug effects; Keratitis, Herpetic; metabolism; pathology; synthesis; Western blotting; Animals; Blotting, Western; Cell Line; Cell Survival; Corneal Neovascularization; Human Umbilical Vein Endothelial Cells; Humans; Keratitis, Herpetic; Male; Mice; Mice, Inbred BALB C; Stigmasterol
Año:2016
Volumen:115
Página de inicio:160
Página de fin:168
DOI: http://dx.doi.org/10.1016/j.steroids.2016.09.001
Título revista:Steroids
Título revista abreviado:Steroids
ISSN:0039128X
CODEN:STEDA
CAS:stigmasterol, 83-48-7; vasculotropin, 127464-60-2; Stigmasterol
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_0039128X_v115_n_p160_Michelini

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Citas:

---------- APA ----------
Michelini, F.M., Lombardi, M.G., Bueno, C.A., Berra, A., Sales, M.E. & Alché, L.E. (2016) . Synthetic stigmasterol derivatives inhibit capillary tube formation, herpetic corneal neovascularization and tumor induced angiogenesis: Antiangiogenic stigmasterol derivatives. Steroids, 115, 160-168.
http://dx.doi.org/10.1016/j.steroids.2016.09.001
---------- CHICAGO ----------
Michelini, F.M., Lombardi, M.G., Bueno, C.A., Berra, A., Sales, M.E., Alché, L.E. "Synthetic stigmasterol derivatives inhibit capillary tube formation, herpetic corneal neovascularization and tumor induced angiogenesis: Antiangiogenic stigmasterol derivatives" . Steroids 115 (2016) : 160-168.
http://dx.doi.org/10.1016/j.steroids.2016.09.001
---------- MLA ----------
Michelini, F.M., Lombardi, M.G., Bueno, C.A., Berra, A., Sales, M.E., Alché, L.E. "Synthetic stigmasterol derivatives inhibit capillary tube formation, herpetic corneal neovascularization and tumor induced angiogenesis: Antiangiogenic stigmasterol derivatives" . Steroids, vol. 115, 2016, pp. 160-168.
http://dx.doi.org/10.1016/j.steroids.2016.09.001
---------- VANCOUVER ----------
Michelini, F.M., Lombardi, M.G., Bueno, C.A., Berra, A., Sales, M.E., Alché, L.E. Synthetic stigmasterol derivatives inhibit capillary tube formation, herpetic corneal neovascularization and tumor induced angiogenesis: Antiangiogenic stigmasterol derivatives. Steroids. 2016;115:160-168.
http://dx.doi.org/10.1016/j.steroids.2016.09.001