noscapine and Skin-Neoplasms

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.

Topics: Binding Sites; Cell Death; Cell Line, Tumor; Circular Dichroism; Esterases; Fluorescence Resonance Energy Transfer; Humans; Hydrophobic and Hydrophilic Interactions; In Vitro Techniques; Molecular Docking Simulation; Molecular Dynamics Simulation; Noscapine; Protein Binding; Protein Interaction Domains and Motifs; Protein Structure, Secondary; Serum Albumin, Human; Skin Neoplasms; Spectroscopy, Fourier Transform Infrared; Static Electricity; Thermodynamics

Noscapine (Nos) and reduced brominated analogue of noscapine (Red-Br-Nos) prevent cellular proliferation and induce apoptosis in cancer cells either alone or in combination with other chemotherapeutic drugs. However, owing to poor physicochemical properties, Nos and Red-Br-Nos have demonstrated their anticancer activity at higher and multiple doses. Therefore, in present investigation, silver nanocrystals of noscapinoids (Nos-Ag. Nos-Ag. Preliminary investigations substantiated that Nos-Ag

Topics: Animals; Antineoplastic Agents; Apoptosis; Cell Line; Cell Line, Tumor; Cell Proliferation; Drug Delivery Systems; Humans; Melanoma; Melanoma, Cutaneous Malignant; Melanoma, Experimental; Mice; Mitochondria; Nanoparticles; Noscapine; Silver; Skin Neoplasms