Modulatory effects of quercetin on proliferation and differentiation of the human colorectal cell line Caco-2

Dihal, Ashwin A.; Woutersen, Ruud A.; Ommen, Ben van; Rietjens, Ivonne M.C.M.; Stierum, Rob H.

doi:10.1016/j.canlet.2005.07.007

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Volume 238, Issue 2 , Pages 248-259, 18 July 2006

Modulatory effects of quercetin on proliferation and differentiation of the human colorectal cell line Caco-2

Ashwin A. Dihal
- Physiological Sciences Department, TNO Quality of Life, Zeist, The Netherlands
- Division of Toxicology, Wageningen University, Wageningen, The Netherlands
- Corresponding author. Physiological Sciences Department, TNO Quality of Life, P.O. Box 360, Postpunt 8, 3700 AJ Zeist, The Netherlands. Tel.: +31 30 6944193; fax: +31 30 6960264.
Ruud A. Woutersen
- Department of Toxicology and Applied Pharmacology, TNO Quality of Life, Zeist, The Netherlands
Ben van Ommen
- Physiological Sciences Department, TNO Quality of Life, Zeist, The Netherlands
Ivonne M.C.M. Rietjens
- Division of Toxicology, Wageningen University, Wageningen, The Netherlands
Rob H. Stierum
- Physiological Sciences Department, TNO Quality of Life, Zeist, The Netherlands

Received 26 May 2005; received in revised form 8 July 2005; accepted 10 July 2005.

Abstract

The effect of the dietary flavonoid quercetin was investigated on proliferation and differentiation of the human colon cancer cell line Caco-2. Confluent Caco-2 monolayers exposed to quercetin showed a biphasic effect on cell proliferation and a decrease in cell differentiation (0.001<P<0.05). During differentiation Caco-2 cells formed 5 phase II metabolites, of which the amount of 4′-O-methyl-quercetin-3′-O-glucuronide correlated with the differentiation grade (r=0.99, P<0.003). The increment of cell proliferation at low quercetin concentrations and the decrease in cell differentiation are effects opposite to what would be expected for a functional food ingredient with anti-carcinogenic potential.

Keywords: Quercetin, Proliferation, Differentiation, Metabolism, Colorectal cancer, Caco-2

Abbreviations used:: ALP, alkaline phosphatase, BrdU, bromo-2′-deoxyuridine, CRC, colorectal cancer, HPLC, high performance liquid chromatography, TEER, trans epithelial electrical resistance