Quercetin-3-methyl Ether Suppresses Proliferation of Mouse Epidermal JB6 P+ Cells by Targeting ERKs

Overview

Journal Carcinogenesis

Specialty Oncology

Date 2011 Dec 6

PMID 22139441

Citations 9

Authors

Jixia Li

Madhusoodanan Mottamal

Haitao Li

Kangdong Liu

Feng Zhu

Yong-Yeon Cho

Carlos P Sosa

Keyuan Zhou

G Tim Bowden

Ann M Bode

Zigang Dong

Affiliations

Soon will be listed here.

Abstract

Chemoprevention has been acknowledged as an important and practical strategy for the management of skin cancer. Quercetin-3-methyl ether, a naturally occurring compound present in various plants, has potent anticancer-promoting activity. We identified this compound by in silico virtual screening of the Traditional Chinese Medicine Database using extracellular signal-regulated kinase 2 (ERK2) as the target protein. Here, we showed that quercetin-3-methyl ether inhibited proliferation of mouse skin epidermal JB6 P+ cells in a dose- and time-dependent manner by inducing cell cycle G(2)-M phase accumulation. It also suppressed 12-O-tetradecanoylphorbol-13-acetate-induced neoplastic cell transformation in a dose-dependent manner. Its inhibitory effect was greater than quercetin. The activation of activator protein-1 was dose-dependently suppressed by quercetin-3-methyl ether treatment. Western blot and kinase assay data revealed that quercetin-3-methyl ether inhibited ERKs kinase activity and attenuated phosphorylation of ERKs. Pull-down assays revealed that quercetin-3-methyl ether directly binds with ERKs. Furthermore, a loss-of-function ERK2 mutation inhibited the effectiveness of the quercetin-3-methyl ether. Overall, these results indicated that quercetin-3-methyl ether exerts potent chemopreventive activity by targeting ERKs.

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