Quercetin-3-methyl ether suppresses proliferation of mouse epidermal JB6 p+ cells by targeting ERKs

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

Research output: Contribution to journalArticle

21 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)459-465
Number of pages7
JournalCarcinogenesis
Volume33
Issue number2
DOIs
StatePublished - 2012

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