The role of bax in pmc-f induced cell death mechanism in HCT116 colon carcinoma cell lines

Levent, Elif (2010) The role of bax in pmc-f induced cell death mechanism in HCT116 colon carcinoma cell lines. [Thesis]

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In a previous study reported from our lab, 2 analogous of Pramanicin (PMC); PMC-A and PMC-F were found to be the most toxic drugs in HCT116 colon carcinoma cell line, among 9 analogues. In this study, cytotoxicity of PMC-A and PMC-F has been compared and death signaling pathways have been identified in HCT116 WT and Bax-/- cells. Bax-/- cells exhibited resistance in the early times of drug treatment, followed similar death response with WT cells. PMC-F was more effective than PMC-A inducing the initial cleavage of caspase-3, -9 and -8. Therefore, PMC-F was used in the further experiments. To understand the role of MAP kinases in PMC-F induced apoptosis, their phosphorylation levels were investigated. The results showed that Bax-/- cells exhibited higher level of ERK 1/2 and JNK phosphorylations. Also, WT cells presented an increasing phosphorylation level of p38 sustained longer than Bax-/- cells. We also demonstrated that PMC-F induced ROS production in both cell lines, but less and with a delayed manner in Bax-/- cells. These data indicate that PMC-A and PMC-F may stand for new potential anti-cancer drugs for the treatment of colon cancer. Moreover, ROS might be the key signaling mechanism which determines the level of MAPK phosphorylation and the earlier resistance of HCT116 Bax-/- cells to death in PMC-F induced apoptosis.
Item Type: Thesis
Uncontrolled Keywords: PMC-F. -- Apoptosis. -- MAPK signaling. -- ROS production. -- HCT116 cell lines. -- PMC-F. -- Apoptoz. -- MAPK sinyalizasyonu. -- ROS üretimi. -- HCT116 hücre hatları.
Subjects: T Technology > TA Engineering (General). Civil engineering (General) > TA164 Bioengineering
Divisions: Faculty of Engineering and Natural Sciences > Academic programs > Biological Sciences & Bio Eng.
Faculty of Engineering and Natural Sciences
Depositing User: IC-Cataloging
Date Deposited: 19 Apr 2012 15:00
Last Modified: 26 Apr 2022 09:55

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