Synthetic stigmasterol derivatives inhibit capillary tube formation, herpetic corneal neovascularization and tumor induced angiogenesis: Antiangiogenic stigmasterol derivatives

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 end...

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Autores principales:	Michelini, F.M., Lombardi, M.G., Bueno, C.A., Berra, A., Sales, M.E., Alché, L.E.
Formato:	JOUR
Materias:	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 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 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 Human Umbilical Vein Endothelial Cells Humans Male Mice Mice, Inbred BALB C Stigmasterol
Acceso en línea:	http://hdl.handle.net/20.500.12110/paper_0039128X_v115_n_p160_Michelini
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

id	todo:paper_0039128X_v115_n_p160_Michelini
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spelling	todo:paper_0039128X_v115_n_p160_Michelini2023-10-03T14:49:19Z Synthetic stigmasterol derivatives inhibit capillary tube formation, herpetic corneal neovascularization and tumor induced angiogenesis: Antiangiogenic stigmasterol derivatives Michelini, F.M. Lombardi, M.G. Bueno, C.A. Berra, A. Sales, M.E. Alché, L.E. 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 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. Fil:Michelini, F.M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Lombardi, M.G. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Bueno, C.A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Alché, L.E. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_0039128X_v115_n_p160_Michelini
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	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
spellingShingle	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 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
topic_facet	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
description	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.
format	JOUR
author	Michelini, F.M. Lombardi, M.G. Bueno, C.A. Berra, A. Sales, M.E. Alché, L.E.
author_facet	Michelini, F.M. Lombardi, M.G. Bueno, C.A. Berra, A. Sales, M.E. Alché, L.E.
author_sort	Michelini, F.M.
title	Synthetic stigmasterol derivatives inhibit capillary tube formation, herpetic corneal neovascularization and tumor induced angiogenesis: Antiangiogenic stigmasterol derivatives
title_short	Synthetic stigmasterol derivatives inhibit capillary tube formation, herpetic corneal neovascularization and tumor induced angiogenesis: Antiangiogenic stigmasterol derivatives
title_full	Synthetic stigmasterol derivatives inhibit capillary tube formation, herpetic corneal neovascularization and tumor induced angiogenesis: Antiangiogenic stigmasterol derivatives
title_fullStr	Synthetic stigmasterol derivatives inhibit capillary tube formation, herpetic corneal neovascularization and tumor induced angiogenesis: Antiangiogenic stigmasterol derivatives
title_full_unstemmed	Synthetic stigmasterol derivatives inhibit capillary tube formation, herpetic corneal neovascularization and tumor induced angiogenesis: Antiangiogenic stigmasterol derivatives
title_sort	synthetic stigmasterol derivatives inhibit capillary tube formation, herpetic corneal neovascularization and tumor induced angiogenesis: antiangiogenic stigmasterol derivatives
url	http://hdl.handle.net/20.500.12110/paper_0039128X_v115_n_p160_Michelini
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Synthetic stigmasterol derivatives inhibit capillary tube formation, herpetic corneal neovascularization and tumor induced angiogenesis: Antiangiogenic stigmasterol derivatives

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