In Vitro Cytotoxicity and Interaction of Noscapine with Human Serum Albumin: Effect on Structure and Esterase Activity of HSA

化学 人血清白蛋白 费斯特共振能量转移 圆二色性 荧光 循环伏安法 生物物理学 光化学 立体化学 生物化学 物理化学 电化学 生物 电极 量子力学 物理
作者
Neha Maurya,Jitendra Kumar Maurya,Upendra Kumar Singh,Ravins Dohare,Md. Zafaryab,M. Moshahid A. Rizvi,Meena Kumari,Rajan Patel
出处
期刊:Molecular Pharmaceutics [American Chemical Society]
卷期号:16 (3): 952-966 被引量:110
标识
DOI:10.1021/acs.molpharmaceut.8b00864
摘要

Noscapine is effective to inhibit cellular proliferation and induced apoptosis in nonsmall cell, lung, breast, lymphoma, and prostate cancer. It also shows good efficiency to skin cancer cells. In the current work, we studied the mechanism of interaction between the anticancer drug noscapine (NOS) and carrier protein human serum albumin (HSA) by using a variety of spectroscopic techniques (fluorescence spectroscopy, time-resolved fluorescence, UV–visible, fluorescence resonance energy transfer (FRET), Fourier transform infrared (FTIR), and circular dichroism (CD) spectroscopy), electrochemistry (cyclic voltammetry), and computational methods (molecular docking and molecular dynamic simulation). The steady-state fluorescence results showed that fluorescence intensity of HSA decreased in the presence of NOS via a static quenching mechanism, which involves ground state complex formation between NOS and HSA. UV–visible and FRET results also supported the fluorescence result. The corresponding thermodynamic result shows that binding of NOS with HSA is exothermic in nature, involving electrostatic interactions as major binding forces. The binding results were further confirmed through a cyclic voltammetry approach. The FRET result signifies the energy transfer from Trp214 of HSA to the NOS. Molecular site marker, molecular docking, and MD simulation results indicated that the principal binding site of HSA for NOS is site I. Synchronous fluorescence spectra, FTIR, 3D fluorescence, CD spectra, and MD simulation results reveal that NOS induced the structural change in HSA. In addition, the MTT assay study on a human skin cancer cell line (A-431) was also performed for NOS, which shows that NOS induced 80% cell death of the population at a 320 μM concentration. Moreover, the esterase-like activity of HSA with NOS was also done to determine the variation in protein functionality after binding with NOS.
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