Study of the controversial resveratrol that interact with the endogenous glutathione thiyl radical in cancer cells

Found in various natural food products, many in vitro evidence indicated that resveratrol (RES) has been linked to neuroprotective and cardioprotective effects and prevent cancer development. However, human clinical trials have been conducted with varying results, making the usage of RES controversial. In this paper, we demonstrated that the drug RES could be conjugated with the high levels of endogenous GSin cancer cells. 5,5-Dimethyl-1-Pyrroline-N-Oxide (DMPO) was employed to capture the GS•. The molecular mechanism of the reaction between RES and GSwas further studied by UV-Vis spectrometry, mass spectrometry and Density Functional Theory (DFT) calculations. Besides, the formation of the adduct GS-RES in cancer cell was obtained when RES was added during incubation. Further study indicated that over 77.6% of the RES was consumed in cancer cells. This study suggested that endogenous GSmay be one of the important factors to cause the depletion of anti-tumour drugs during chemotherapy, which should be paid special attention in clinical therapeutics and drug development.