Investigation of the pro-apoptotic and anti-metastatic effects of myrtus communis (myronic plant) on human osteosarcoma cells (SAOS-2) under in-vitro conditions

Cancer is one of the most important health problems of today, increasing day by day, threatening life in many ways and causing material and moral losses. Chemotherapy, radiotherapy and surgical methods are used for the treatment of cancer. Patients treated with chemotherapy may experience some significant adverse side effects. Various side effects such as nausea, vomiting, diarrhea, hair loss, loss of appetite, fatigue, fever, mouth sores, and pain may occur. For this reason, the importance of new treatment strategies to reduce the side effects of chemotherapy or as an alternative to chemotherapy in the treatment of cancer is increasing. Plant-derived compounds tested on various tumor types may provide strategies for further cancer therapy. In this thesis, the effect of Myrtus Communis L. (Myrtle) plant extract on the osteosarcoma (Saos-2) cell line, which is the most malignant and most common type of primary bone tumors, was investigated. In the study, the mechanisms associated with apoptosis, inflammation and oxidative stress and the biomolecules that play a role in these mechanisms were examined. MTT (3-(4,5-dimethyl-thiazolyl)-2,5-diphenyltetrazolium bromide) test for cytotoxicity analysis, ELISA test for determination of cytokine (TNF-α, IL-10, IL-12, IFN-γ) levels, Photometric tests for oxidative stress (TAS and TOS) and real-time PCR for apoptosis were used. It was determined that the 50% inhibiting dose (IC50) was 1/1.28 dilution in Saos-2 cells treated with different concentrations of Myrtus Communis extracts for 24 hours. It was determined that Myrtus Communis extract applied at this concentration increased the levels of inflammatory cytokines (TNF-α, IL-12 and IFN-γ), decreased the level of the anti-inflammatory cytokine IL-10, and these changes were statistically significant. Significant increases were detected in the total antioxidant level (TAS), total oxidant level (TOS) and oxidative stress index (OSI) levels in the treatment group. It was determined that the plant extract statistically significantly increased the mRNA expression levels of Bax, Bcl-2, Caspase-3, Caspase-9, p53, p21 genes and the apoptotic index determined by Bax/Bcl-2 ratio. While the expression level of the MMP-2 gene, which plays a role in metastasis, increased at a statistically insignificant level, MMP-9 gene expression could not be determined. The results obtained from this study suggest that it may be possible to use M. Communis together with chemotherapeutics in the treatment of the disease, since it induces apoptosis in osteosarcoma cells. In order to confirm and/or support this idea, further in vivo and in vitro studies are needed in this direction.