Fagonia arabica-based gold nanoparticles and its phytochemicals against triple-negative breast cancer

Abstract

According to WHO, Breast cancer is the most widespread form of cancer worldwide and the fifth-leading cause of death from cancer. In Pakistan, breast cancer is the most frequent type of cancer in terms of both incidence and fatality. Among all the major types of breast cancer, Triple Negative Breast Cancer (TNBC) is the most evasive, recurrent, and difficult to treat. TNBC lacks almost all major hormonal receptors as well as other therapeutic targets that were used in targeted therapy. Cases of TNBC constitutes almost 15% of total breast cancer worldwide and in Pakistan this percentage is even higher up to 24%. Conventional treatments of TNBC are surgery, Chemotherapy, Radiotherapy and Targeted approaches. Conventional therapies to treat TNBC have a lot of disadvantages in terms of less efficacy, high recurrence rate, high cost, low aesthetic value, off target effects, and difficult availability. Due to all these effects new therapeutic approaches are continuously studied like targeted inhibition by novel bioactive plant compounds and nanomedicine. A major portion of already available drugs come from plant sources so it’s natural to seek further interest in bio-active compounds from plant sources. One such ethnomedicinal plant is Fagonia arabica, that is used in this study against TNBC. Nanomedicine is also another new technique used in breast cancer therapeutic as well as diagnostics. One of the most common nanoparticles utilized in medicine is called gold nanoparticles (AuNPs), because of their bioactive and biocompatible nature. AuNPs are used as therapeutic agents as well as drug delivery vehicles. In this study Fagonia arabica was collected and whole plant extract was prepared by Soxhlet method. The extract was used to prepare AuNPs by green synthesis method. AuNPs were characterized using UV-Vis, SEM, EDS, XRD, and FTIR. All the techniques used confirmed the formation of AuNPs and their surface functionalization with plant phytochemicals. Bioactivity assays were performed on both AuNPs as well as plant extract. Antioxidant potential was confirmed using DPPH. Both AuNPs and Plant extract showed excellent Antioxidant potential. Anti-inflammatory effects were studied using Protein Denaturation assays. Both samples scored excellent in this test. Phytochemical constituents of plant extracts were analyzed using GC-MS techniques. Total 250 Compounds were identified. Bioactive compounds were shortlisted based on Insilco Drug Discovery parameters like Lipinsky rules, ADMET properties, Lead likeliness, HERG analysis, Cardiotoxicity etc. 6 Compounds were shortlisted based on perfect druggable properties. The XV topmost responsible HUB genes of TNBC were isolated using online database and HUB gene analysis. 3D protein structures of Top 3 Hub genes were docked with All 6 compounds using PyRx software and compound 3 showed excellent affinity with low docking energy. A short simulation of Docked proteins was done using Cabflex 2.0 online server indicating flexibility and stability of protein structures. Lastly invitro therapeutic effect of Plant extract and AuNPs was studied on TNBC by using MTT Assay on MDA-MB-231 cell lines indicating dose dependent cytotoxic response from both samples. This study proved the potential of Fagonia arabica against TNBC, specifically its bioactive compounds like 1-(4-Hydroxy-5,5-dimethyl-2- oxo-3-phenylimidazolidin-1-yl)-3-phenylurea. It also proved the bioactive potential of green synthesized AuNPs. Further studies are required to provide further evidence