FUNGAL KAYNAKLI BASSİATİN’İN (3R,6R) MEME KANSERİ HÜCRE HATLARI ÜZERİNDEKİ ETKİSİNİN ARAŞTIRILMASI

Abstract

Cancer causes millions of deaths which is considered as one of the most important diseases of our century. It causes psychologically debilitating effects in advanced stages as well as physical damages to the body. Scientists conduct variety of research on this subject for the treatment of this disease that affects human life adversely and leads to deaths. It is seen that Studies have focused on factors influencing the type of cancer and cancer development. Treatment varies according to the type of cancer. Because there are many internal and external factors that trigger the growth and proliferation of cancer according to organs and tissues. The most effective one in the cancer treatment is called conventional chemotherapy, the substances obtained by synthetic or naturally are used to kill cancer cells. Generally, the substances used in the chemotherapy of cancer, are effective without distinguishing between normal cells and cancer cells. However, the substances are tried to be discovered on the target tissue with studies. It is required that these substances should eliminate only the cancer cells without affecting normal cells. Nowadays, many substances are investigated with in vitro and in vivo studies towards the target. However, very few of these substances are currently utilized in the treatment of cancer. Breast cancer which the most common type of cancer in women is the leading cause of cancer deaths. Therefore, early diagnosis and effective treatment are extremely important. Although breast cancer is treated with cytotoxic chemotherapy drugs, the patient's normal body cells are damaged and the quality of life is impaired in this treatment. Therefore, the studies are continuing to find the substance for the effective treatment of breast cancer without any affect to other normal cells. Especially, the anti-estrogenic agents ‘Tamoxifen’ which prevents the effect of 17ß-oestradiol on estrogen receptor bearing (ER +) breast cancer cells, is widely used in breast cancer patients. However, tamoxifen is an expensive product and the cells begin to develop resistance. That’s why, this situation encourages science world to find a new and more effective alternative agent. Bassiatin (3R,6R) which is produced by some fungi (eg entomopathogenic fungus Beauveria bassiana), is a depsipeptid based on morpholine. In recent studies show that bassiatin has an anti-estrogenic effect and it stops the proliferation of ER + MCF-7 breast cancer cell line. In this study following this aim, firstly bassiatin was produced using entomopathogenic fungi Beauveria bassiana, Fusarium oxysporum and Paecilomyces fumosoroseus species and it was provided to obtain bassiatin as pure. After that, bassiatin's inhibition and cytotoxicity was examined on MCF-7 cancer cell line derived from mammary tissue and apoptosis mechanism of this cell line was discussed in terms of activation. To compare the effect of this substance on receptors with this cell line, cytotoxicity tests were conducted with MDA-MB-231 and SK-BR-3 breast cancer cell lines. The relationship between bassiatin with epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor (VEGFR) was examined that recognize effective factors in the development of breast cancer cells, in addition to the estrogen receptor in this cancer cell line. The findings obtained as a result of this study, it was shown that bassiatin can be used effectively in breast cancer treatment because of both its simple production and selective cell inhibition. Progressive studies should be considered as one of the treatment options for clinical breast cancer cases.