In-silico method for elucidation of prodigiosin as PARP-1 inhibitor a prime target of Triple-negative breast cancer.

Triple-Negative Breast Cancer (TNBC) is found to be one of the life-threatening cancer. Poly (ADP-Ribose) Polymerase-1 (PARP-1) is overexpressed by those tumour cells, which become resistant to chemotherapies. Inhibition of PARP-1 has a considerable effect on treating TNBC. Prodigiosin is a valuable pharmaceutical compound that exhibits anticancer properties. The present study aims to virtually evaluate prodigiosin as a potent PARP-1 inhibitor using Molecular docking and Molecular Dynamics (MD) simulation studies. The PASS (Prediction of Activity Spectra for Substances) prediction tool evaluated the biological properties of prodigiosin. Then the drug-likeness and pharmacokinetic properties of prodigiosin were determined using Swiss-ADME software. It was suggested that prodigiosin obeyed Lipinski's rule of five and thus could act as a drug with good pharmacokinetic properties. Moreover, molecular docking was done with AutoDock 4.2 to identify the critical amino acids of the protein-ligand complex. It was indicated that prodigiosin has a docking score of -8.08 kcal/mol, which showed its effective interaction with crucial amino acid, His201A of PARP-1 protein. Further, MD simulation was performed using Gromacs software to validate the stability of the prodigiosin-PARP-1 complex. Prodigiosin was found to have good structural stability and affinity at the active site of PARP-1 protein. Additionally, PCA and MM-PBSA were calculated for the prodigiosin-PARP-1 complex, which revealed that prodigiosin has an excellent binding affinity towards PARP-1 protein. Prodigiosin can possibly be used as oral drug due to its PARP-1 inhibition through high binding affinity, structural stability, and receptor flexibility towards crucial amino acid residue His201A of PARP-1 protein. In-addition, in-vitro cytotoxicity, and apoptosis analysis of prodigiosin-treated TNBC cell line-MDA-MB-231 revealed that prodigiosin exhibited significant anticancer activity in 101.1 µg/mL concentration, when compared to commercially available synthetic drug cisplatin. Thus, prodigiosin could act as a potential candidate for treatment of TNBC than the commercially available synthetic drugs.

Eco-Friendly Preparation of Silver Nanoparticles and Their Antiproliferative and Apoptosis-Inducing Ability against Lung Cancer.

In the present study, the anti-proliferative and apoptotic potential of Tabebuia roseo-alba in lung cancer was assessed. Silver nanoparticles (AgNPs) of T. roseo-alba were synthesized using an ethanolic extract and characterized by adopting various parameters. Herein, the eco-friendly, cost-effective, and green synthesis of AgNPs was evaluated using an ethanolic extract of T. roseo-alba. The as-synthesized AgNPs were then characterized using various characterization techniques, such as UV-visible spectroscopy (UV-vis), X-ray powder diffraction (XRD), dynamic light scattering (DLS), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). The AgNPs are crystalline, spherical, and highly stable AgNPs of varying sizes in the range of 5-20 nm. The anticancer activity of the ethanolic extract of T. roseo-alba and its AgNPs was determined using an MTT assay. The results indicated that, although both samples showed prominent anti-proliferative activity on lung cancer cell lines, the AgNPs of T. roseo-alba were found to be more potent than the ethanolic extract. Further, apoptosis induction ability was evaluated by FITC Annexin V and PI staining, the results of which demonstrated the efficiency of the ethanolic extract of T. roseo-alba and its AgNPs in causing oxidative stress and subsequent cellular death. This was subsequently further confirmed by measuring the mitochondrial membrane potential after staining the cells with JC1. The apoptotic mode of cell death was further confirmed by DNA fragmentation and caspase assays using Western blot analysis.