Department of Biology, Faculty of Sciences, Islamic Azad University, Mashhad Branch, Mashhad, Iran.
Department of Medicinal Chemistry, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
DNA Cell Biol. 2021 Aug;40(8):1039-1051. doi: 10.1089/dna.2021.0052. Epub 2021 Jun 24.
The interaction of calf thymus DNA (ct DNA) with anastrozole, which is acknowledged as an antineoplastic drug, has been enquired into in the absence and presence of histone H1, through the means of absorbance, fluorescence, circular dichroism spectroscopy, viscosity, thermal melting, and molecular modeling techniques. In addition, the effects of anastrozole on MCF 7 cell line have been thoroughly investigated. Fluorescence spectroscopy results have indicated that quenching mechanism of ct DNA-anastrozole are known as static quenching procedures, since the Stern-Volmer quenching constant (K) seems to face a decrease as the temperature is enhanced; this is a significant evidence for intercalative binding mode of anastrozole with ct DNA. Regarding the ternary system in the presence of H1, the constant of Stern-Volmer quenching was increased as the temperature was heightened. The thermodynamic parameters suggested that the binding could be characterized as exothermic by negative and positive enthalpy and entropy changes in both binary and ternary systems, respectively. It is vital to mention that hydrogen bonds and hydrophobic contributions play significant roles in anastrozole association to ct DNA in the absence and presence of H1. In accordance to the absorption spectroscopy and melting temperature curve outcomes, the binding mode of anastrozole with ct DNA in absence and presence of H1 was indicative of intercalative and nonintercalative bindings, respectively. The viscosity results as binary and ternary systems, which have been elucidated from a sensitive viscometer, have confirmed the fluorescence spectroscopy determinations. The intercalation of anastrozole to ct DNA seemed to be significantly related to an induced reduction in MCF-7 cell proliferation. The molecular modeling results have suggested that anastrozole could bind to H1 in ct DNA-H1 complex in ternary systems, which supports the conclusions that have been obtained from experimental data.
在缺乏和存在组蛋白 H1 的情况下，通过吸收、荧光、圆二色性光谱、粘度、热融和分子建模技术研究了小牛胸腺 DNA（ctDNA）与被认为是抗肿瘤药物的阿那曲唑的相互作用。此外，还深入研究了阿那曲唑对 MCF-7 细胞系的影响。荧光光谱结果表明，ctDNA-阿那曲唑的猝灭机制是静态猝灭过程，因为 Stern-Volmer 猝灭常数（K）似乎随着温度的升高而降低；这是阿那曲唑与 ctDNA 以插入方式结合的重要证据。对于存在 H1 的三元体系，随着温度的升高，Stern-Volmer 猝灭常数增加。热力学参数表明，在二元和三元体系中，结合可以分别通过负和正焓和熵变化来表征为放热。值得一提的是，氢键和疏水贡献在阿那曲唑与 ctDNA 的结合中起着重要作用，无论是否存在 H1。根据吸收光谱和熔解温度曲线的结果，阿那曲唑与 ctDNA 的结合模式在缺乏和存在 H1 的情况下分别指示为插入和非插入结合。二元和三元体系的粘度结果，通过灵敏的粘度计阐明，证实了荧光光谱的测定。阿那曲唑与 ctDNA 的插入似乎与 MCF-7 细胞增殖的诱导减少密切相关。分子建模结果表明，阿那曲唑可以与三元体系中 ctDNA-H1 复合物中的 H1 结合，这支持了从实验数据得出的结论。
