Enhancement of human cancer cell radiosensitivity by conjugated eicosapentaenoic acid - a mammalian DNA polymerase inhibitor

Mizushina
2010 International Journal of Oncology  
We previously found that conjugated eicosapentaenoic acid (cEPA) selectively inhibited the activities of mammalian DNA polymerases (pols), and suppressed human cancer cell growth. The aim of the present study was to evaluate the efficacy of concurrent radiation with cEPA in a human colon carcinoma cell line, HCT 116. Furthermore, we examined the most effective timing of irradiation. The postirradiation addition of cEPA significantly enhanced HCT116 cell radiosensitivity by decreasing the
more » ... creasing the expression of pols ß, ‰ and Â, increasing damaged DNA, such as DNA double-strand breaks, inhibiting clonogenic survival, and inducing apoptosis. However, cells treated by pre-irradiation addition of cEPA did not influence radiosensitive survival and radiation-induced apoptosis. cEPA inhibited the activities of pols needed for DNA repair, thereby DNA damage must be augmented by cEPA and irradiation. These results suggested that the combination of inhibitors of DNA repair-related pols/radiation could be an effective anticancer therapy. Abbreviations: cEPA, conjugated eicosapentaenoic acid; pol, DNA polymerase (EC 2.7.7.7); DSB, DNA double-strand break; PUFA, polyunsaturated fatty acid; ATR, ataxia-telangiectasia mutated-and Rad3-related protein kinase; MTT, 3-(4,5dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; PCR, polymerase chain reaction
doi:10.3892/ijo_00000532 fatcat:kmeik3rnevhxdigsbsr7c3uxee