Assessment of Phytochemicals in Preventing Oxidatively Damaged DNA in Bladder Cancer

Oxidatively damaged DNA is thought to be important in both the initiation and development of bladder carcinoma. Phytochemical compounds are thought to promote optimal health, partly via their antioxidant effects in protecting cellular components against damaging free radicals. The objective of this study is to assess the effect of a standardised bilberry extract, mirtoselect, on the level of endogenous and induced oxidatively damaged DNA in bladder cancer cells, as assessed by the Comet assay. The Comet assay, also known as single-cell gel electrophoresis, represents a simple method for measuring DNA strand break damage in eukaryotic cells. The sensitivity and specificity of the assay is greatly enhanced by the addition of bacterial repair endonucleases that recognise specific types of damage in the DNA and converts these lesions into additional DNA breaks. - Studies of mirtoselect against three bladder cancer cell lines (RT112, RT4 and HT1376) have shown significant antiproliferative activities against RT112 cells and against RT4 cells (p<0.05), but not against HT1376 cells. The treatment of all bladder cancer cell lines with mirtoselect (50 µg/ml) for a duration of seven days did not lower the level of endogenous oxidatively damaged DNA as detected by the modified endonuclease-alkaline Comet assay. However, a significant level of protection was observed when exogenous hydrogen peroxide was used to induce oxidatively damaged DNA in all the bladder cancer cell lines studied. Further studies revealed that mirtoselect may possibly mediate its antioxidant property through metal chelation, rather than free radical scavenging. - Our studies demonstrated that mirtoselect was potent enough to reduce levels of exogenously-induced oxidatively damaged DNA in the bladder cancer cell lines studied. Additionally, the ability of mirtoselect to reduce bladder cancer cells proliferation further highlights anthocyanins as promising future chemopreventive agents against bladder cancer.