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

Abstract

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 GS^• in 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 GS^• was 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 GS^• may 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.

Keywords:

• Glutathione
• glutathione thiyl radical
• Density Functional Theory
• resveratrol

Acknowledgments

This research did not receive any specific grant from funding agencies.

Disclosure statement

The authors declare no conflict of interest.