4.6 Article

Determining the Interaction Behavior of Calf Thymus DNA with Anastrozole in the Presence of Histone H1: Spectroscopies and Cell Viability of MCF-7 Cell Line Investigations

期刊

DNA AND CELL BIOLOGY
卷 40, 期 8, 页码 1039-1051

出版社

MARY ANN LIEBERT, INC
DOI: 10.1089/dna.2021.0052

关键词

calf thymus DNA; anastrozole; spectroscopy; thermodynamics; molecular modeling; binding mode

资金

  1. Research Council of the Mashhad Branch, Islamic Azad University, and Mashhad University of Medical Sciences

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The interaction between calf thymus DNA and anastrozole was studied, indicating a potential intercalative binding mode. The presence of histone H1 increased the Stern-Volmer quenching constant, showing exothermic binding behavior. Hydrogen bonds and hydrophobic contributions play significant roles in anastrozole association with DNA, potentially inhibiting cell proliferation.
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-SV) 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.

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