EVALUATION OF THE PROTECTİVE EFFECT OF EXOSOMES AGAİNİST COLCHICINE CYTOTOXICITY IN HEPG-2 CELL LİNE MODEL
Project no. 30817 · Status: Kapanmış (Yayın bekleniyor) · 2023
Summary
<p>Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality worldwide. Current targeted or immunotherapeutic drugs used in the treatment of HCC primarily aim to slow tumor progression and extend survival rather than cure the disease. Additionally, the high cost and significant side effects associated with these treatments underscore the need for an effective, affordable, and well-tolerated drug for HCC therapy. Colchicine, a natural alkaloid derived from the Colchicum autumnale plant, is distinguished by its anti-inflammatory, antifibrotic, and therapeutic properties. It is widely utilized in the treatment of hereditary diseases such as Familial Mediterranean Fever (FMF), as well as gout, Behçet's disease, pericarditis, and various fibrotic conditions. By inhibiting microtubule polymerization, colchicine disrupts cell mitosis and arrests the cell cycle at metaphase. Through its apoptosis-inducing and antifibrotic properties, colchicine is also considered a potential anticancer agent. While oral administration of colchicine is considered safe when used appropriately and contraindications are excluded, its clinical application as an anticancer agent has been limited due to severe drug interactions, organ failure, morbidity, toxicity, and a very narrow therapeutic index. Exosomes are nanoscale extracellular vesicles produced under normal physiological and pathological conditions, characterized by unique features such as low immunogenicity, long circulation half-life, significant tissue penetration, and biocompatibility. Exosomes can carry biologically active molecules such as nucleic acids and proteins and serve as intercellular messengers by delivering their contents to target cells. Given these properties, exosome-based therapies for cancer have been a prominent focus of research for a considerable time.</p><p>In this thesis, the aim was to investigate the anticancer effects of colchicine-loaded exosomes derived from AM-MKH and to evaluate both the drug delivery capabilities of the exosomes and the impact of encapsulated colchicine on HepG2 cells. Within this scope, the IC50 values of pure colchicine and the Exo-Col formulation were determined, and their effects on cell proliferation and apoptosis in the HepG2 cell line were experimentally assessed. The findings revealed that the Exo-Col formulation exhibited significantly higher anticancer efficacy at lower doses compared to pure colchicine. Notably, exosomes were observed to enhance the efficient delivery of colchicine to cells and contribute to a more specific therapeutic effect. These results support the potential of exosomes as an effective drug delivery system and demonstrate their promise as a novel approach for targeted therapies.</p>