Antitumor effects of cyano-substituted organic compounds in vitro

Majsec, Kristina (2010) Antitumor effects of cyano-substituted organic compounds in vitro. Diploma thesis, Faculty of Science > Department of Biology.

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The discovery of novel potential chemotherapeutics has become one of the most important goals in medical chemistry. Here, mechanisms of actions are researched for two novel cyanoderivatives with a cytotoxic effect on HeLa cell line. These potent antitumor agents are cyanosubstituted naphtothiophene (compound 1) and cyano-substituted thieno-thiophenecarboxanilide (compound 2). It is has been previously reported that both compounds induce G1 arrest and apoptosis after 24h and 48h. Here, we measured an increase in activation of caspase-3 in HeLa cells after 48 h treatment for both compounds. Compound 2 additionally induced apoptosis by activation of poly(ADP-ribose) polymerase 1 (PARP-1). In order to elucidate the mechanism through which these compounds induce G1 arrest, Western blot analysis of cell cycle regulators, p53, p21 and p27, was performed. It was shown that both compounds act in a p53-independent manner. Compound 1 increases p21 and p27 expression, while compound 2 decreases expression of these proteins. The disruption of cytoskeletal networks of actin and tubulin for both compounds was established by fluorescence microscopy. Western blot analysis also showed deregulation of expression of cytoskeletal proteins by compound 1. Measurement of reactive oxygen species (ROS) formation showed stronger antioxidative effect of compound 2 on HeLa cells. Major mechanism of action, in spite of strong similarities, was not found. This research partially elucidated molecular aspects of action of cyano-substituted heteroaryls in HeLa cell line.

Item Type: Thesis (Diploma thesis)
Keywords: cyano-substitued heteroaryles, apoptosis, cell cycle, cytoskelet, antioxidans
Supervisor: Ester, Katja
Co-supervisor: Matulić, Maja
Date: 2010
Number of Pages: 56
Subjects: NATURAL SCIENCES > Biology
Divisions: Faculty of Science > Department of Biology
Depositing User: Silvana Šehić
Date Deposited: 04 Sep 2014 10:37
Last Modified: 04 Sep 2014 10:37

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