Coffee Phenolic Phytochemicals Suppress Colon Cancer Metastasis by Targeting MEK and TOPK
Open accessAbstract
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.
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Caffeic acid has a direct effect on inhibition of ERK phosphorylation, with downregulation of neoplastic transformation of JB6 P1 cells.
“As with caffeine, a direct effect of CA has been shown on the inhibition of ERK phosphorylation, with the result of the downregulation of the neoplastic transformation of JB6 P1 cells [84].”
From Effects of Coffee and Its Components on the Gastrointestinal Tract and the Brain–Gut Axis (2020) · cites this paper as [84]
The ERK/p90RSK phosphorylation section reports that caffeic acid inhibited TPA-induced ERK phosphorylation, and the JB6 P+ transformation results report reduced neoplastic transformation. The sentence’s comparison with caffeine is not supported by this paper: its transformation results say caffeine had no effect (Figure 5). (LLM, conf=0.88)
Experimental — accuracy not yet measuredCoffee consumption of over 1 cup daily in colon cancer patients has been associated with significant attenuation of ERK, a kinase directly involved in development of colon cancer.
“In this way, coffee consumption of over 1 cup of coffee daily in colon cancer patients has been associated with a significant attenuation of ERK, a kinase directly involved in the development of colon cancer [84].”
From Effects of Coffee and Its Components on the Gastrointestinal Tract and the Brain–Gut Axis (2020) · cites this paper as [84]
CA strongly suppresses the activity of MEK1 and TOPK, and binds directly to either MEK1 or TOPK in an ATP-noncompetitive manner.
“CA strongly suppresses the activity of mitogen-activated MAPK/ERK kinase (MEK1), a protein kinase whose constitutive activation results in cell transformation, and TOPK, a serine/threonine kinase expressed in high levels in CRC and an activator of ERKs. CA binds directly to either MEK1 or lymphokine-activated killer t-cell-originated protein kinase-like protein (TOPK) in an ATP-noncompetitive mann”
From Effects of Coffee and Its Components on the Gastrointestinal Tract and the Brain–Gut Axis (2020) · cites this paper as [84]
In mice, CA administration inhibits lung metastasis induced by infusion of CT-26 colon cancer cells.
“Kang et al. (2011) [84] showed that lung metastasis induced in mice by infusion of CT-26 colon cancer cells are inhibited after CA administration.”
From Effects of Coffee and Its Components on the Gastrointestinal Tract and the Brain–Gut Axis (2020) · cites this paper as [84]
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- Authors
- 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.
- Affiliations
- University of Minnesota (US)
- Seoul National University (KR)
- Konkuk University (KR)
- Mayo Clinic (US)
- Corresponding author
- Dong, Zigang
- ORCID
- Venue
- Carcinogenesis
- Publisher
- Oxford University Press (OUP)
- Published
- 2011-02-11
- Volume
- 32
- Issue
- 6
- Pages
- 921-928
- ISSN
- 0143-3334 (ISSN-L)
- 1460-2180
- PMC
- PMC3106432
- OpenAlex
- W2137762121
- Cited by
- 123
- References
- 48
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 8 · 2023: 8 · 2022: 9 · 2021: 16 · 2020: 8 · 2019: 6 · 2018: 11 · 2017: 14 · 2016: 7 · 2015: 4 · 2014: 8 · 2013: 9 · 2012: 7
- FWCI
- 6.09
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Carcinogenesis (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Hormel Foundation (CA111536, CA077646)
- National Institutes of Health (CA111536, CA027502)
- National Cancer Institute (CA 120388, R01CA111536, CA 077646, R01CA120388, CA027502, R01CA077646, R01CA081064, R37CA081064, CA111536, CA081064, P01CA027502)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK084567)
- Topics
- Health Sciences › Medicine › Pharmacology › Coffee research and impacts
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Melanoma and MAPK Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics, phytochemicals, and oxidative stress
- Keywords
- coffee, caffeic acid, colon cancer metastasis, MEK1, TOPK, ERK1/2 phosphorylation, chemoprevention, phenolic phytochemicals, lung metastasis, AP-1 transactivation, NF-κB transactivation, oncogenic transformation, caffeine, chlorogenic acid
- MeSH terms
- Adenocarcinoma, Animals, Cell Adhesion, Cell Transformation, Neoplastic, Chlorogenic Acid, Coffee, Colonic Neoplasms, Humans, Immunoenzyme Techniques, Luciferases, Lung Neoplasms, Male, Mice, Inbred BALB C, Models, Molecular, Phenols, Prospective Studies, Blotting, Western, Protein Serine-Threonine Kinases, Matrix Metalloproteinase 2, Matrix Metalloproteinase 9, Mitogen-Activated Protein Kinase Kinases, Xenograft Model Antitumor Assays, Mice
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