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DOI: 10.1055/s-0034-1394876
Ursolic acid: A chemopreventive agent for DNA damage associated diseases
Diet is an important factor in colorectal cancer. Although some dietary habits have been associated with cancer promotion, for example high-fat diets, diets rich in fruits and vegetables have shown preventive potential. A recent study from our lab showed in vitro chemopreventive effects of natural compounds by protection against oxidative DNA damage and stimulation of DNA repair. It demonstrated that ursolic acid (UA), a natural compound found in apples and prunes, protects DNA from oxidative damage and also increases repair activity in Caco-2 cells and that these protective effects could contribute to its anti-carcinogenic potential [1]. However, the in vitro effects of compounds are not always seen in vivo. In order to verify its in vivo efficacy, we evaluated the effects of 2 week dietary supplementation with UA or epigallocatechin gallate (EGCG), main compound of green tea, on DNA damage in colonocytes and lymphocytes isolated from Fischer 344 rats. DNA damage (strand breaks, oxidized and alkylated bases) was evaluated using the Comet assay. Also, MMS was used, ex vivo, to investigate the potential of our natural compounds to protect against alkylating damage. This study demonstrated that endogenous DNA damage in colonocytes was slightly higher than in lymphocytes. UA and EGCG decreased the levels of endogenous DNA damage in colonocytes, while in lymphocytes only UA had this effect. Treatment with MMS showed a tendency to increase DNA damage but was not significant. UA protected against MMS-induced DNA damage, while EGCG did not show protective effects. UA and EGCG protected colonocytes and lymphocytes against DNA damage. These results suggest that UA can protect DNA from both endogenous and induced DNA damage in both cell types, while EGCG was found to protect only against endogenous DNA damage in colonocytes. This study proved that the in vitro chemopreventive effects of UA, demonstrated in a previous study by our group, are also seen in vivo. This affirm UA as a possible chemopreventive agent for DNA damage associated diseases.
Acknowledgements: This work is supported by national funds by FCT – Portuguese Foundation for Science and Technology, under the project PEst-OE/AGR/UI4033/2014, and by the FCT grant SFRH/BD/64817/2009.
References:
[1] A. Ramos, C. Pereira-Wilson, and A. Collins, (2010) Protective effects of ursolic acid and luteolin against oxidative DNA damage include enhancement of DNA repair in Caco-2 cells., Mutat. Res., vol. 692, no. 1 – 2, pp. 6 – 11.