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      Inhibitory Effect of 2′-O-Benzoylcinnamaldehyde on Vascular Endothelial Cell Proliferation and Migration

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          Abstract

          Purpose: To evaluate the inhibitory effect of the farnesyl transferase inhibitor 2′-O-benzoylcinnamaldehyde (CB 2′-ph) on proliferation and migration of vascular endothelial cells. Methods: Bovine lens epithelial cells, bovine corneal endothelial cells, bovine keratocytes, bovine aortic endothelial cells (BAECs) and human umbilical vein endothelial cells (HUVECs) were treated with CB 2′-ph to determine its cell type specificity and antiproliferative effect. For inhibition of vascular endothelial cell growth factor (VEGF)- or basic fibroblast growth factor (bFGF)-induced proliferation of HUVECs, these cells were treated with various concentrations of CB 2′-ph. To assess the proliferation, MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide) assay was used. The migration assay was also performed to determine the effect of CB 2′-ph on HUVECs. The distance of HUVEC outgrowth was measured from the scraped edge of a monolayer after treatment with CB 2′-ph concentrations of 0, 1.5 and 2.5 µg/ml for 24, 48 and 72 h. Results: The CB 2′-ph had an inhibitory effect on all tested types of cell proliferation but only HUVEC and BAEC proliferation was specifically inhibited in a dose-dependent manner. In addition, CB 2′-ph inhibited VEGF- or bFGF-induced proliferation and migration of HUVECs in a dose-dependent manner. Conclusions: These results indicate that CB 2′-ph, a farnesyl transferase inhibitor is thought to be an effective inhibitor of vascular endothelial cell proliferation and migration.

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          Integrin αvβ3 Requirement for Sustained Mitogen-activated Protein Kinase Activity during Angiogenesis

          Angiogenesis depends on growth factors and vascular cell adhesion events. Integrins and growth factors are capable of activating the ras/MAP kinase pathway in vitro, yet how these signals influence endothelial cells during angiogenesis is unknown. Upon initiation of angiogenesis with basic fibroblast growth factor (bFGF) on the chick chorioallantoic membrane (CAM), endothelial cell mitogen-activated protein (MAP) kinase (ERK) activity was detected as early as 5 min yet was sustained for at least 20 h. The initial wave of ERK activity (5–120 min) was refractory to integrin antagonists, whereas the sustained activity (4–20 h) depended on integrin αvβ3, but not β1 integrins. Inhibition of MAP kinase kinase (MEK) during this sustained αvβ3-dependent ERK signal blocked the formation of new blood vessels while not influencing preexisting blood vessels on the CAM. Inhibition of MEK also blocked growth factor induced migration but not adhesion of endothelial cells in vitro. Therefore, angiogenesis depends on sustained ERK activity regulated by the ligation state of both a growth factor receptor and integrin αvβ3.
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            Angiogenesis inhibition: a review.

            In this review we discuss the concept of anti-angiogenesis, which is the inhibition of neovascularization. Anti-angiogenic agents are viewed from the standpoint of their effect on various elements of the angiogenic process, including induction of vascular discontinuity, endothelial cell movement, endothelial cell proliferation, and three-dimensional restructuring of patent vessels. An effort is made to place the many different approaches to anti-angiogenesis research into a comprehensible structure, in order to identify problems of evaluation and interpretation, thereby providing a clearer basis for determining promising and needed directions for further investigation.
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              Suppression of Nerve Growth Factor-induced Neuronal Differentiation of PC12 Cells

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                Author and article information

                Journal
                ORE
                Ophthalmic Res
                10.1159/issn.0030-3747
                Ophthalmic Research
                S. Karger AG
                0030-3747
                1423-0259
                2001
                April 2001
                05 March 2001
                : 33
                : 2
                : 111-116
                Affiliations
                aDepartment of Ophthalmology and Visual Science, Catholic Research Institute of Medical Science, The Catholic University of Korea, College of Medicine, bKorea Research Institute of Bioscience and Biotechnology, Seoul, Korea
                Article
                55654 Ophthalmic Res 2001;33:111–116
                10.1159/000055654
                11244358
                © 2001 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                Page count
                Figures: 4, References: 23, Pages: 6
                Categories
                Original Paper

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