Effect of Resveratrol and Mixtures of Resveratrol and Mitomycin C on Cancer Cells under Irradiation

Abstract

The radiation-biological effects of resveratrol (Res) alone or with mitomycin C (MMC) were investigated under various conditions in human breast cancer cells (MCF-7). The data of the survival curves obtained in aerated media (acting species: 42% OH, 54% O₂^.-) showed that Res possesses antitumor activity and also acts as an efficient radical scavenger. This property was extremely enhanced in the presence of MMC. In media saturated with N₂O (90% OH, 10% H) Res at low concentrations acted as a radiation-protecting agent, but at higher concentrations its cytostatic effect predominated. At the same time, the MMC-activity was reduced. In anaerobic media, Res demonstrated its radiation-protecting ability, but in mixtures the MMC-ability was reduced in comparison to that of pure MMC due to competition reactions between Res and MMC for the available free radicals. Finally, in a cell suspension containing formate as a specific scavenger for OH and H radicals (pH=7.4), Res successfully competed for these species and showed antitumor activity. Considering the reaction rate constants of the involved substrates and the implemented concentrations in each medium, the kinetic probability of each survival curve was calculated. Based on these data it was evident that the bifunctional property of Res (acting as radiation protector and also having antitumor activity) was based on an electron ejection process from its excited single state and on its reactivity with the primary radicals (OH, H, e_aq^-).