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.

摘要

在各种天然食品中发现的许多体外证据表明，白藜芦醇 (RES) 与神经保护和心脏保护作用以及预防癌症发展有关。然而，已经进行的人体临床试验产生了不同的结果，使得 RES 的使用存在争议。在本文中，我们证明了药物 RES 可以与癌细胞中高水平的内源性 GS ^{• 结合}。5,5-二甲基-1-吡咯啉-N-氧化物(DMPO) 用于捕获GS ^•。RES与GS反应的分子机制^•通过紫外-可见光谱法、质谱法和密度泛函理论 (DFT) 计算进一步研究。此外，在孵育过程中加入RES时，在癌细胞中形成了加合物GS-RES。进一步的研究表明，超过 77.6% 的 RES 被癌细胞消耗。本研究提示，内源性GS ^•可能是导致化疗期间抗肿瘤药物耗竭的重要因素之一，临床治疗和药物开发中应特别注意。