Banerjee Soma, Chaudhuri Siddhi, Maity Anup Kumar, Saha Partha, Pal Samir Kumar
Department of Chemical, Biological & Macromolecular Sciences, S. N. Bose National Centre for Basic Sciences, Block JD, Sector III, Salt Lake, Kolkata, 700 098, India.
J Mol Recognit. 2014 Aug;27(8):510-20. doi: 10.1002/jmr.2379.
Electron transfer (ET) reactions are important for their implications in both oxidative and reductive DNA damages. The current contribution investigates the efficacy of caffeine, a xanthine alkaloid in preventing UVA radiation induced ET from a carcinogen, benzo[a]pyrene (BP) to DNA by forming stable caffeine-BP complexes. While steady-state emission and absorption results emphasize the role of caffeine in hosting BP in aqueous medium, the molecular modeling studies propose the energetically favorable structure of caffeine-BP complex. The picosecond-resolved emission spectroscopic studies precisely explore the caffeine-mediated inhibition of ET from BP to DNA under UVA radiation. The potential therapeutic activity of caffeine in preventing DNA damage has been ensured by agarose gel electrophoresis. Furthermore, time-gated fluorescence microscopy has been used to monitor caffeine-mediated exclusion of BP from various cell lines including squamous epithelial cells, WI-38 (fibroblast), MCF-7 (breast cancer) and HeLa (cervical cancer) cells. Our in vitro and ex vivo experimental results provide imperative evidences about the role of caffeine in modified biomolecular recognition of a model carcinogen BP by DNA resulting dissociation of the carcinogen from various cell lines, implicating its potential medicinal applications in the prevention of other toxic organic molecule induced cellular damages.
电子转移(ET)反应因其在氧化性和还原性DNA损伤中的作用而具有重要意义。本研究探讨了黄嘌呤生物碱咖啡因通过形成稳定的咖啡因 - 苯并[a]芘(BP)复合物来预防UVA辐射诱导的致癌物BP向DNA的电子转移的功效。稳态发射和吸收结果强调了咖啡因在水性介质中容纳BP的作用,而分子建模研究提出了咖啡因 - BP复合物的能量有利结构。皮秒分辨发射光谱研究精确地探索了在UVA辐射下咖啡因介导的从BP到DNA的电子转移抑制作用。琼脂糖凝胶电泳已证实咖啡因在预防DNA损伤方面的潜在治疗活性。此外,时间分辨荧光显微镜已用于监测咖啡因介导的BP从包括鳞状上皮细胞、WI - 38(成纤维细胞)、MCF - 7(乳腺癌)和HeLa(宫颈癌)细胞在内的各种细胞系中的排除。我们的体外和体内实验结果提供了关于咖啡因在DNA对模型致癌物BP的修饰生物分子识别中的作用的重要证据,导致致癌物从各种细胞系中解离,暗示其在预防其他有毒有机分子诱导的细胞损伤方面的潜在医学应用。