American Association for Cancer Research
Browse
19406207capr140141-sup-130849_1_supp_0_n7cs52.pdf (68.85 kB)

Supplemental Figure Legend from Caffeic Acid Directly Targets ERK1/2 to Attenuate Solar UV-Induced Skin Carcinogenesis

Download (68.85 kB)
journal contribution
posted on 2023-04-03, 19:23 authored by Ge Yang, Yang Fu, Margarita Malakhova, Igor Kurinov, Feng Zhu, Ke Yao, Haitao Li, Hanyong Chen, Wei Li, Do Young Lim, Yuqiao Sheng, Ann M. Bode, Ziming Dong, Zigang Dong

Supplemental Figure Legend

History

ARTICLE ABSTRACT

Caffeic acid (3,4-dihydroxycinnamic acid) is a well-known phenolic phytochemical present in coffee and reportedly has anticancer activities. However, the underlying molecular mechanisms and targeted proteins involved in the suppression of carcinogenesis by caffeic acid are not fully understood. In this study, we report that caffeic acid significantly inhibits colony formation of human skin cancer cells and EGF-induced neoplastic transformation of HaCaT cells dose-dependently. Caffeic acid topically applied to dorsal mouse skin significantly suppressed tumor incidence and volume in a solar UV (SUV)–induced skin carcinogenesis mouse model. A substantial reduction of phosphorylation in mitogen-activated protein kinase signaling was observed in mice treated with caffeic acid either before or after SUV exposure. Caffeic acid directly interacted with ERK1/2 and inhibited ERK1/2 activities in vitro. Importantly, we resolved the cocrystal structure of ERK2 complexed with caffeic acid. Caffeic acid interacted directly with ERK2 at amino acid residues Q105, D106, and M108. Moreover, A431 cells expressing knockdown of ERK2 lost sensitivity to caffeic acid in a skin cancer xenograft mouse model. Taken together, our results suggest that caffeic acid exerts chemopreventive activity against SUV-induced skin carcinogenesis by targeting ERK1 and 2. Cancer Prev Res; 7(10); 1056–66. ©2014 AACR.

Usage metrics

    Cancer Prevention Research

    Licence

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC