Skip Navigation



eCAM Advance Access published online on April 7, 2009
eCAM, doi:10.1093/ecam/nep024
This Article
Right arrow Full Text Freely available
Right arrow Full Text (PDF) Freely available
Right arrow E-letters: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when E-letters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Google Scholar
Right arrow Articles by Kunimasa, K.
Right arrow Articles by Ohta, T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kunimasa, K.
Right arrow Articles by Ohta, T.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?


© 2009 The Author(s).
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Brazilian Propolis Suppresses Angiogenesis by Inducing Apoptosis in Tube-forming Endothelial Cells through Inactivation of Survival Signal ERK1/2

Kazuhiro Kunimasa1,*, Mok-Ryeon Ahn1,{dagger}, Tomomi Kobayashi1, Ryoji Eguchi2, Shigenori Kumazawa1, Yoshihiro Fujimori3, Takashi Nakano2, Tsutomu Nakayama1, Kazuhiko Kaji1 and Toshiro Ohta1,*

1Graduate School of Nutritional and Environmental Sciences and Global COE Program, University of Shizuoka, Shizuoka 422-8526, 2Department of Thoracic Oncology, Hyogo College of Medicine and 3Cancer Center, Hyogo College of Medicine, Hyogo 663-8501, Japan

We recently reported that propolis suppresses tumor-induced angiogenesis through tube formation inhibition and apoptosis induction in endothelial cells. However, molecular mechanisms underlying such angiogenesis suppression by propolis have not been fully elucidated. The aim of this study was to investigate the effects of ethanol extract of Brazilian propolis (EEBP) on two major survival signals, extracellular signal-regulated kinase 1/2 (ERK1/2) and Akt, and to elucidate whether changes in these signals were actually involved in antiangiogenic effects of the propolis. Detection by western blotting revealed that EEBP suppressed phosphorylation of ERK1/2, but not that of Akt. Pharmacological inhibition by U0126 demonstrated that ERK1/2 inactivation alone was enough to inhibit tube formation and induce apoptosis. It was also shown that EEBP and U0126 similarly induced activation of caspase-3 and cleavage of poly ADP-ribose polymerase (PARP) and lamin A/C, all of which are molecular markers of apoptosis. These results indicate that inhibition of survival signal ERK1/2, and subsequent induction of apoptosis, is a critical mechanism of angiogenesis suppression by EEBP.

Keywords: caspase-3 – human umbilical vein endothelial cells – tube formation – U0126

For reprints and all correspondence: Toshiro Ohta, Graduate School of Nutritional and Environmental Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka-shi, Shizuoka 422-8526, Japan. Tel/Fax: +81-54-264-5571; E-mail: ohtat{at}u-shizuoka-ken.ac.jp

*These authors contributed equally to this work.

{dagger}Current address: Dept. of Food and Nutrition, Dong-A University, 840 Hadan-2 dong, Saha-gu, Busan 604-714, Korea.

Received October 8, 2008; accepted March 3, 2009


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.