Linalool-Loaded Glutathione-Modified Gold Nanoparticles Conjugated with CALNN Peptide as Apoptosis Inducer and NF-κB Translocation Inhibitor in SKOV-3 Cell Line

• Published in: International journal of nanomedicine 2020-01, Vol.15, p.9025-9047
• Main Authors: Jabir, Majid, Sahib, Usama I, Taqi, Zainab, Taha, Ali, Sulaiman, Ghassan, Albukhaty, Salim, Al-Shammari, Ahmed, Alwahibi, Mona, Soliman, Dina, Dewir, Yaser Hassan, Rizwana, Humaira
• Format: Article
• Language: English
• Subjects: Acyclic Monoterpenes - chemistry; Antineoplastic Agents - pharmacology; Antioxidants - pharmacology; Apoptosis; Apoptosis - drug effects; Biomarkers, Tumor - metabolism; Breast cancer; calnn; Caspase 8 - genetics; Caspase 8 - metabolism; caspase-8; Cell growth; Cell Line, Tumor; Cell Nucleus Shape - drug effects; Cytotoxicity; DNA Damage; Down-Regulation - drug effects; Down-Regulation - genetics; Flow cytometry; Gene Expression Regulation, Neoplastic - drug effects; Glutathione - chemistry; Gold - chemistry; gold nanoparticles; Humans; linalool; Membrane Potential, Mitochondrial - drug effects; Metal Nanoparticles - chemistry; Metal Nanoparticles - ultrastructure; Microscopy; Morphology; Mutagens - toxicity; Nanoparticles; NF-kappa B - metabolism; nf-κb translocation; Oils & fats; Original Research; Ovarian cancer; p53; Peptides; Peptides - pharmacology; Protein Transport - drug effects; skov-3; Tumor Suppressor Protein p53 - genetics; Tumor Suppressor Protein p53 - metabolism; Up-Regulation - drug effects; Up-Regulation - genetics
• ISSN: 1178-2013; 1176-9114; 1178-2013
• DOI: 10.2147/IJN.S276714

Linalool is a monoterpene compound with various potential therapeutic applications in several medical fields. Previous studies have indicated the activity of linalool against cell lines; however, its high level of toxicity restricts its use. The aim of this study was to design and manufacture compounds with a novel structure that can be used for loading linalool, to reduce its toxicity and improve its reachable ability. We synthesized and characterized a new molecule for loading linalool onto gold nanoparticles (GNPs) capped with glutathione and conjugated with a CALNN peptide. Linalool was loaded onto the GNPs via the reaction of the surface groups of both linalool and the GNPs. Moreover, the target peptide could be loaded onto the surface of the GNPs via a chemical reaction. The cytotoxic effects of linalool-GNP (LG) and linalool-GNP-CALNN peptide (LGC) conjugates against ovarian cancer cells were investigated, as were the possible mechanisms underlying the induction of apoptosis. Our findings illustrated the significant antiproliferative effect of LG and LGC on SKOV-3 cells. The cytotoxicity assay demonstrated that LG and LGC were selectively toxic in cancer cells and induced apoptosis by activating caspase-8, the p53 protein, and various proteins involved in apoptosis. The present data demonstrated that LG and LGC have a high therapeutic potential and should be given particular consideration as anticancer drug-delivery systems, as LG and LGC were remarkably more cytotoxic against a cancer cell line than were linalool and GNPs alone. We concluded that LG and LGC are promising compounds that can be used for treating ovarian cancer (SKOV-3) cells via the induction of apoptosis through extrinsic and intrinsic pathways.