Skip Navigation



Carcinogenesis Advance Access published online on August 11, 2007
Carcinogenesis, doi:10.1093/carcin/bgm110
This Article
Right arrow Advance Access manuscript (PDF) Freely available
Right arrow All Versions of this Article:
28/9/1918    most recent
bgm110v1
Right arrow Alert me when this article is cited
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
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Lee, K. W.
Right arrow Articles by Dong, Z.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lee, K. W.
Right arrow Articles by Dong, Z.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2007. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Myricetin is a novel natural inhibitor of neoplastic cell transformation and MEK1

Ki Won Lee1,2,3, Nam Joo Kang1,4, Evgeny A. Rogozin1, Hong-Gyum Kim1, Yong Yeon Cho1, Ann M. Bode1, Hyong Joo Lee4, Young-Joon Surh3, G Tim Bowden5 and Zigang Dong1,*

1 Hormel Institute, University of Minnesota, MN 55912, USA
2 Department of Bioscience and Biotechnology and IBST, Konkuk University, Seoul 143-701, Republic of Korea
3 College of Pharmacy
4 School of Agricultural Biotechnology, Seoul National University, Seoul 151-742, Republic of Korea
5 Arizona Cancer Center, The University of Arizona, AZ85724-5024, USA

* To whom correspondence should be addressed at: Hormel Institute, University of Minnesota, 801 16th Avenue NE, Austin, MN 55912. Tel: 507-437-9600; Fax: 507-437-9606; E-mail: zgdong{at}hi.umn.edu.

Evidence suggests that MEK plays a role in cell transformation and tumor development and might be a significant target for chemoprevention. 3,5,4'-Trihydroxy-trans-stilbene (resveratrol), a non-flavonoid polyphenol found in various foods and beverages, including red wines, is reported to be a natural chemopreventive agent. However, the concentrations required to exert these effects might be difficult to achieve by drinking only one or two glasses of red wine a day. On the other hand, the flavonol content of red wine is about 30 times higher than resveratrol. Here we demonstrated that 3,3',4',5,5',7-hexahydroxyflavone (myricetin), one of the major flavonols in red wine, is a novel inhibitor of MEK1 activity and transformation of JB6 P+ mouse epidermal cells. Myricetin (10 µM) inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA) or epidermal growth factor (EGF)-induced cell transformation by 76% or 72%, respectively, compared to respective reductions of 26% or 19% by resveratrol (20 µM). A combination of myricetin and resveratrol exerted additive but not synergistic effects on either TPA- or EGF-induced transformation. Myricetin, but not resveratrol, attenuated tumor promoter-induced activation of c-fos or activator protein-1. Myricetin strongly inhibited MEK1 kinase activity and suppressed TPA- or EGF-induced phosphorylation of ERK or p90RSK, downstream targets of MEK. Moreover, myricetin inhibited H-Ras-induced cell transformation more effectively than either PD098059, a MEK inhibitor, or resveratrol. Myricetin directly bound with GST-MEK1 but did not compete with ATP. Overall, these results indicated that myricetin has potent anticancer-promoting activity and mainly targets MEK signaling, which may contribute to the chemopreventive potential of several foods including red wines.

Key Words: Myricetin • MEK1 • neoplastic transformation • AP-1

Received January 5, 2007; revised April 27, 2007; accepted April 27, 2007.


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


This article has been cited by other articles:


Home page
 Cancer Res.Home page
S. K. Jung, K. W. Lee, S. Byun, N. J. Kang, S. H. Lim, Y.-S. Heo, A. M. Bode, G. T. Bowden, H. J. Lee, and Z. Dong
Myricetin Suppresses UVB-Induced Skin Cancer by Targeting Fyn
Cancer Res., July 15, 2008; 68(14): 6021 - 6029.
[Abstract] [Full Text] [PDF]


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.