Novel chemosensitizer effect of the antibacterial agent dmc-deb005 through inhibition of autophagy
Başlık çevirisi mevcut değil.
- Tez No: 838535
- Danışmanlar: DR. KATALİN KOVáCS
- Tez Türü: Yüksek Lisans
- Konular: Moleküler Tıp, Mikrobiyoloji, Tıbbi Biyoloji, Molecular Medicine, Microbiology, Medical Biology
- Anahtar Kelimeler: Belirtilmemiş.
- Yıl: 2024
- Dil: İngilizce
- Üniversite: Debrecenı Egyetem
- Enstitü: Yurtdışı Enstitü
- Ana Bilim Dalı: Belirtilmemiş.
- Bilim Dalı: Belirtilmemiş.
- Sayfa Sayısı: Belirtilmemiş.
Özet
Autophagy is the process of self-eating which involves the degradation of cellular elements and recycling of the building blocks. A basal level of autophagy is necessary to keep cells free of damaged proteins and organelles. Defective autophagy is observed in many human diseases. However, autophagy plays a dual role in tumorigenesis and in cancer treatment responsiveness. While in the early stages of cancer development, autophagy has a predominantly protective role restricting carcinogenesis, in the more advanced phases, it stimulates cancer growth and spreading. It has been proposed that autophagy inhibitors may potentiate the anticancer effect of various chemotherapeutic agents. Previously we carried out a DALGreen-based high-content screening of 775 FDA-approved compounds and identified an antibacterial agent (DMC-Deb005) as a drug that reduces the rate of autophagy in A549 cells. To better understand the effect of autophagy on cancer, we applied this drug to the A459 adenocarcinoma cell line in a combined treatment with 5-fluorouracil and etoposide as anticancer agents. We measured cell viability using MTT assay. Combined treatment resulted in reduced viability of cancer cells, compared to treatments with anticancer agents only. The combined treatment also decreased the long-term proliferation rate of cells measured with sulphorodamin B assay. We also tested the effect of the compound in a 3D cell culture (spheroid) assay. We observed that the cells with combined treatment displayed improper formation of cellular spheroids and more pronounced spheroid disruption have also been observed. In conclusion, DMC-Deb005 and the anticancer agents have synergistic effects on cancer cell death in our model. Supervisors: Dr. Kovács Katalin, Prof. Dr. Virág László
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