Coffee phenolic phytochemicals suppress colon cancer metastasis by targeting MEK and TOPK

Nam Joo Kang, Ki Won Lee, Bo Hyun Kim, Ann M. Bode, Hyo Jeong Lee, Yong Seok Heo, Lisa Boardman, Paul Limburg, Hyong Joo Lee, Zigang Dong

Research output: Contribution to journalArticle

63 Scopus citations

Abstract

Epidemiological studies suggest that coffee consumption reduces the risk of cancers, including colon cancer, but the molecular mechanisms and target(s) underlying the chemopreventive effects of coffee and its active ingredient(s) remain unknown. Based on serving size or daily units, coffee contains larger amounts of phenolic phytochemicals than tea or red wine. Coffee or chlorogenic acid inhibited CT-26 colon cancer cell-induced lung metastasis by blocking phosphorylation of ERKs. Coffee or caffeic acid (CaA) strongly suppressed mitogen-activated MEK1 and TOPK activities and bound directly to either MEK1 or TOPK in an ATP-noncompetitive manner. Coffee or CaA, but not caffeine, inhibited ERKs phosphorylation, AP-1 and NF-κB transactivation and subsequently inhibited TPA-, EGF- and H-Ras-induced neoplastic transformation of JB6 P+ cells. Coffee consumption was also associated with a significant attenuation of ERKs phosphorylation in colon cancer patients. These results suggest that coffee and CaA target MEK1 and TOPK to suppress colon cancer metastasis and neoplastic cell transformation.

Original languageEnglish (US)
Pages (from-to)921-928
Number of pages8
JournalCarcinogenesis
Volume32
Issue number6
DOIs
StatePublished - 2011

ASJC Scopus subject areas

  • Cancer Research

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    Kang, N. J., Lee, K. W., Kim, B. H., Bode, A. M., Lee, H. J., Heo, Y. S., Boardman, L., Limburg, P., Lee, H. J., & Dong, Z. (2011). Coffee phenolic phytochemicals suppress colon cancer metastasis by targeting MEK and TOPK. Carcinogenesis, 32(6), 921-928. https://doi.org/10.1093/carcin/bgr022