Research has shown that there is a geographical distribution of cancer throughout the world caused by lifestyle factors, for example diet. Generally, red meat, excess of calories and saturated fats have been shown to increase the risk for developing cancer, whereas fruit, vegetables and fibers have been shown to decrease this risk. However, the risk of hormones present in food in relation to (hormone-dependent) cancers is not clarified yet. We investigated the effects of estrogens (E1, E2 and E3) and some of their metabolites (2-OHE2, 4-OHE2, 16aOHE1 and 2-MeOE2) on MCF-7 human mammary carcinoma cells (expressing ERa and ERß) and on CaCo-2 human colon carcinoma cells (poorly expressing ERß and ERa). Cell growth (MTT assay), genotoxicity (Comet assay) and cell cycle status (FACS) were studied after exposure of the cells to the estrogens. The binding affinity of the estrogens to human ERa was studied with the Rikilt Estrogen yeast Assay (REA). None of the estrogens showed clear effects on cell growth in the CaCo-2 cell line, whereas all estrogens induced cell growth in the MCF-7 cell line, with different EC50 values. None of the tested compounds (4-OHE2, 16aOHE1 and E2) were genotoxic at a concentration of 10 µM in both cell lines. Interestingly, 2-MeOE2 induced cell cycle arrest in the G(2)/M phase of the MCF-7 cells. All compounds bound to human ERa, but with different affinity. The observation that the CaCo-2 cells did not give a clear response after exposure to estrogens, whereas the MCF-7 cells did and that all estrogens have been shown to bind to human ERa, suggests that the effects seen are ER(a) dependent. 2-MeOE2 induced cell cycle arrest of MCF-7 cells in the G(2)/M phase, indicating that it acts as an anti-tumor agent. The effects seen in both cell lines are probably not caused by genotoxicity. At the moment, the effects of E2, 2-MeOE2 and 4-OHE2 on gene expression in both cell lines are studied using human whole genome oligo microarrays
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