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Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis
Published on: March 30, 2019
Coffee reduces KRAS expression in Caco-2 human colon carcinoma cells via regulation of miRNAs
Takuya Nakayama1, Megumi Funakoshi-Tago1, Hiroomi Tamura1
1Graduate School of Pharmaceutical Sciences, Keio University, Tokyo 105-8512, Japan.
Abstract:
Previous epidemiological studies have demonstrated that moderate coffee consumption is associated with a lower risk of certain types of cancer, particularly colon cancer. To elucidate the molecular basis for this protective action, the effect of coffee on Caco-2 human colon carcinoma cells was investigated. Low concentrations of coffee (<5%) inhibited proliferation of Caco-2 cells without affecting cell viability. Coffee also reduced KRAS proto-oncogene, GTPase (KRAS) gene expression in a dose-dependent manner; however, caffeine, caffeic acid and chlorogenic acid, three major constituents of coffee, did not exhibit this effect. Increasing the duration of coffee bean roasting increased the reduction in KRAS expression, suggesting that the active constituents responsible for this effect emerged during the roasting process. MicroRNA (miR) analysis revealed that coffee induced the expression of miR-30c and miR-96, both of which target the KRAS gene. The results of the present study suggested that daily coffee consumption may reduce KRAS activity, thereby preventing the malignant growth of colon carcinoma cells.
Insights
Moderate coffee consumption may lower colon cancer risk by inhibiting cancer cell growth. Coffee reduces KRAS gene expression, a key factor in colon carcinoma, through compounds developed during roasting.
Area of Science:
- Oncology
- Molecular Biology
- Nutritional Science
Background:
- Epidemiological studies suggest coffee consumption correlates with reduced cancer risk, especially colon cancer.
- The molecular mechanisms underlying coffee's potential chemopreventive effects remain largely unexplored.
Purpose of the Study:
- To investigate the molecular impact of coffee on Caco-2 human colon carcinoma cells.
- To identify the specific coffee components and processes contributing to its anti-cancer effects.
Main Methods:
- Exposure of Caco-2 cells to varying concentrations of coffee.
- Analysis of cell proliferation, viability, and KRAS gene expression.
- Assessment of the effects of coffee constituents (caffeine, caffeic acid, chlorogenic acid) and roasting duration.
- MicroRNA (miR) expression profiling.
Main Results:
- Low coffee concentrations (<5%) inhibited Caco-2 cell proliferation without affecting viability.
- Coffee dose-dependently reduced KRAS proto-oncogene, GTPase (KRAS) gene expression.
- The reduction in KRAS expression intensified with increased coffee bean roasting duration.
- Coffee upregulated miR-30c and miR-96, both identified as KRAS gene targets.
Conclusions:
- Coffee consumption may inhibit colon carcinoma cell proliferation by downregulating KRAS activity.
- Roasting process generates active compounds in coffee responsible for KRAS modulation.
- Upregulation of specific microRNAs (miR-30c, miR-96) by coffee contributes to KRAS inhibition.
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