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Highly Cytotoxic Cyano-Substitued Compounds: A Search for Mechanism of Antitumor Action (CROSBI ID 574620)

Prilog sa skupa u zborniku | sažetak izlaganja sa skupa | međunarodna recenzija

Majsec, Kristina ; Ester, Katja ; Marjanović, Marko ; Kralj, Marijeta Highly Cytotoxic Cyano-Substitued Compounds: A Search for Mechanism of Antitumor Action // Stem Cells and Cancer, 6. International Heinrich FC Behr Symposium Abstracts. Heidelberg: German Cancer Research Centre, 2010

Podaci o odgovornosti

Majsec, Kristina ; Ester, Katja ; Marjanović, Marko ; Kralj, Marijeta

engleski

Highly Cytotoxic Cyano-Substitued Compounds: A Search for Mechanism of Antitumor Action

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 and cyano-substituted thieno- thiophenecarboxanilide. Both compounds induce G1 arrest and apoptosis after 24h and 48h. Also, we measured an increase in activation of caspase-3 in HeLa cells after 48 h treatment for both compounds. 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 3 increases p21 and p27 expression, while compound 5 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 3. Measurement of reactive oxygen species (ROS) formation showed stronger antioxidative effect of compound 5 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.

cyano-substitued heteroaryles; apoptosis; cell cycle; cytoskelet; antioxidans

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Podaci o prilogu

2010.

objavljeno

Podaci o matičnoj publikaciji

Stem Cells and Cancer, 6. International Heinrich FC Behr Symposium Abstracts

Heidelberg: German Cancer Research Centre

Podaci o skupu

Stem Cells and Cancer, 6. International Heinrich FC Behr Symposium

poster

03.10.2010-05.10.2010

Heidelberg, Njemačka

Povezanost rada

Temeljne medicinske znanosti, Biologija