Ethanol promotes survival and tumor progression of colon cancer cells

In the Western Countries, colon cancer is the third tumor for aggressiveness and incidence after lung andbreast/prostate cancer. Different risk factors concur to the development of colon cancer, including geneticfactors, inflammation, intestinal microflora composition, as well as lifestyle. Epidemiologic studiescorrelating alcohol consumption and assert that the risks are 5-fold higher amongdrinkers compared to nondrinkers. However, the exact mechanisms correlating heavy alcohol drinking andcolon cancer are not completely elucidated yet. To shed light on the biochemical mechanisms through whichalcohol favors colon cancer progression, we evaluated the effect of high doses of ethanol (100 mM and 300mM) on HCT116 and HT29 cells, two human colon cancer cell lines. Our study provided evidence thatethanol did not exert cytotoxic effects on either the cell lines, but rather promoted cell survival andproliferation. Western blot analyses showed that ethanol exposure increased the level of GRP78 and Chop,two markers of endoplasmic reticulum stress. Furthermore our analysis demonstrated that ethanol promotedthe autophagy as a defense mechanism and induced activation of Nrf2, the main regulator of anti-oxidantresponse. These defense mechanisms were correlated with an increase in the metalloprotease activity,making the colon cancer cell phenotype more invasive.