Ethanol promotes survival and tumor progression of colon cancer cells

Abstract

In the Western Countries, colon cancer is the third tumor for aggressiveness and incidence after lung and breast/prostate cancer. Different risk factors concur to the development of colon cancer, including genetic factors, inflammation, intestinal microflora composition, as well as lifestyle. Epidemiologic studies correlating alcohol consumption and assert that the risks are 5-fold higher among drinkers compared to nondrinkers. However, the exact mechanisms correlating heavy alcohol drinking and colon cancer are not completely elucidated yet. To shed light on the biochemical mechanisms through which alcohol favors colon cancer progression, we evaluated the effect of high doses of ethanol (100 mM and 300 mM) on HCT116 and HT29 cells, two human colon cancer cell lines. Our study provided evidence that ethanol did not exert cytotoxic effects on either the cell lines, but rather promoted cell survival and proliferation. 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 promoted the autophagy as a defense mechanism and induced activation of Nrf2, the main regulator of anti-oxidant response. These defense mechanisms were correlated with an increase in the metalloprotease activity, making the colon cancer cell phenotype more invasive.