Investigation of the anti-cancer properties of novel 4'-alkyl substituated klavuzon derivatives on pancreatic cancer cell line için kapak resmi
Investigation of the anti-cancer properties of novel 4'-alkyl substituated klavuzon derivatives on pancreatic cancer cell line
Başlık:
Investigation of the anti-cancer properties of novel 4'-alkyl substituated klavuzon derivatives on pancreatic cancer cell line
Yazar:
Şen, Ayhan, author.
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Fiziksel Tanımlama:
x, 42 leaves:+ 1 computer laser optical disc.
Özet:
In anti-cancer agent studies one of the important issue is to discover an agent that target specifically cancer cells with no or minimal effects on normal cells. (R)-goniothalamin, which is a styryl lactone isolated from plants, is an anti-cancer agent that is cytotoxic to cancer cell lines with no or minimal effect on normal cells. Also klavuzon molecule, the 1-naphthyl substituted 5,6-dihydro-2H-pyran-2-one derivative, was tested on cancer cell lines and showed higher cytotoxicity. In the first part of this study anti-proliferative effect of novel 4’-alkyl substituted klavuzon derivatives were tested on MIA PaCa-2 cancer cell line and normal Human Pancreatic Duct Epithelial Cell (HPDEC) line by using MTT, and it is found that cytotoxic activity of the compounds depends on the size of the substituent at position 4 in 1-naphthyl part. While two of them, methyl and ethyl substituted, showed high cytotoxicity to MIA PaCa-2 that IC50 values in nano-molar levels. Next studies were continued with 4’-methylklavuzon derivative. In the second part, the apoptotic effect and cell cycle analysis of 4’-methylklavuzon was studied. Especially at the 10 μM concentration there was increment in both early and late apoptosis. Cell cycle analysis showed that increasing the concentration of molecule caused cell cycle arrest in S and G2 phases. The next part was testing the inhibitory effect of 4’-methylklavuzon on human topoisomerase I enzyme. This enzyme was chosen as one potential target, because 4’-methylklavuzon caused S and G2 phase arrest. Topo I is an actively working enzyme during S phase and inhibition of its activity causes DNA fragmentation and apoptosis. The results showed that there was time dependent inhibition of Topo I enzyme in vitro. The last part of the study was to show DNA fragmentation at cellular level by COMET assay, also known as Single Cell Gel Electrophoresis. After Topo I assay has showed the Topo I inhibition activity of 4’-methylklavuzon, COMET assay was performed. Especially at the 5 μM concentration comets were formed and tail moments were parallel with positive control.
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Tek Biçim Eser Adı:
Thesis (Master)--İzmir Institute of Technology: Molekuler Biology and Genetics..

İzmir Institute of Technology: Molekuler Biology and Genetics--Thesis(Master).
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