Diet and colon cancer - modulation of signaling pathways and DNA damage prevention

Abstract

Colorectal cancer (CRC) is a common malignancy and significant cause of death in Western societies. It develops through an accumulation of genetic and epigenetic alterations, transforming normal cells and giving them growth advantage. Many food plants are rich in bioactive compounds and have shown to posses anticancer properties. We proposed to explore the effects of sage (Salvia officinalis (SO)) water extract (herbal tea) drinking on CRC prevention. F344 rats were used to study the effects of sage tea drinking on pre-initiation (SO treatment before AOM exposure) and post-initiation (SO after AOM exposure) phases of carcinogenesis. We found a chemopreventive effect of SO in the pre-initiation group, but not in the post-initiation. We then investigated if SO affected AOM metabolism, searching for effects on CYP2E1 expression and activity. We found that AOM decreased CYP2E1 activity when compared with control, but SO treatment before AOM prevented this effect. The capacity of SO in vivo treatment to protect colonocytes from H2O2 damage induced in vitro was also investigated. SO decreased significantly the oxidative H2O2-induced DNA damage. We also searched for alterations in cell proliferation and found that SO reduced the number of Ki67-positive cells in the colon after increase induced by AOM. Sage water extract seems to have the ability to prevent CRC and studies to further explore this potential are ongoing.