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master's thesis
Protutumorski učinci cijano - supstituiranih organskih spojeva in vitro
Zagreb: University of Zagreb, Faculty of Science, 2010. urn:nbn:hr:217:089026
Majsec, Kristina
University of Zagreb
Faculty of Science
Department of Biology

Institutional repository: Repository of the Faculty of Science

Cite this document

Majsec, K. (2010). Protutumorski učinci cijano - supstituiranih organskih spojeva in vitro (Master's thesis). Zagreb: University of Zagreb, Faculty of Science. Retrieved from https://urn.nsk.hr/urn:nbn:hr:217:089026

Majsec, Kristina. "Protutumorski učinci cijano - supstituiranih organskih spojeva in vitro." Master's thesis, University of Zagreb, Faculty of Science, 2010. https://urn.nsk.hr/urn:nbn:hr:217:089026

Majsec, Kristina. "Protutumorski učinci cijano - supstituiranih organskih spojeva in vitro." Master's thesis, University of Zagreb, Faculty of Science, 2010. https://urn.nsk.hr/urn:nbn:hr:217:089026

Majsec, K. (2010). 'Protutumorski učinci cijano - supstituiranih organskih spojeva in vitro', Master's thesis, University of Zagreb, Faculty of Science, accessed 03 May 2024, https://urn.nsk.hr/urn:nbn:hr:217:089026

Majsec K. Protutumorski učinci cijano - supstituiranih organskih spojeva in vitro [Master's thesis]. Zagreb: University of Zagreb, Faculty of Science; 2010 [cited 2024 May 03] Available at: https://urn.nsk.hr/urn:nbn:hr:217:089026

K. Majsec, "Protutumorski učinci cijano - supstituiranih organskih spojeva in vitro", Master's thesis, University of Zagreb, Faculty of Science, Zagreb, 2010. Available at: https://urn.nsk.hr/urn:nbn:hr:217:089026

Metadata
TitleProtutumorski učinci cijano - supstituiranih organskih spojeva in vitro
Title (english)Antitumor effects of cyano-substituted organic compounds in vitro
AuthorKristina Majsec
MentorKatja Ester (mentor)
Committee memberKatja Ester (predsjednik povjerenstva)
Committee memberIta Gruić Sovulj (član povjerenstva)
Committee memberMirta Tkalec (član povjerenstva)
Committee memberMaja Matulić (član povjerenstva)
GranterUniversity of Zagreb
Faculty of Science
(Department of Biology)
Zagreb
Defense date and country2010-10-29, Croatia
Scientific / art field,
discipline and subdiscipline		NATURAL SCIENCES
Biology
Abstract
U današnje vrijeme je potraga za novim kemoterapeuticima postala jedno od najvažnijih područja istraživanja unutar medicinske kemije. U ovom radu istražen je mehanizam rada dvaju novih cijano-supstituiranih heteroarila, koji citotoksično djeluju na staničnu liniju HeLa. Ovdje istraživani antitumorski spojevi su cijano-supstituirani naftotiofen (spoj 1) i cijano-supstituirani tieno-tiofen-karboksanilid (spoj 2). Za oba je spoja prethodno nađeno kako uzrokuju zastoj u fazi G1 i smrt stanica HeLa nakon tretmana u trajanju od 24 i 48 h. Mjerenjem aktivnosti kaspaze-3 pokazano je kako oba spoja povećavaju aktivnost tog enzima u stanicama HeLa nakon 48 h. Spoj 2 dodatno potiče apoptozu aktivacijom poli(ADP-riboza) polimeraza 1 (PARP-1). Kako bi razjasnili mehanizam kojim spojevi zaustavljaju stanični ciklus u fazi G1, metodom Western blot promatrana je razina ekspresije proteina regulatora staničnog ciklusa p53, p21 i p27. Ovime je pokazano kako oba spoja djeluju neovisno o p53. Spoj 1 povećava ekspresiju proteina p21 i p27, dok spoj 2 smanjuje njihovu ekspresiju. Fluorescencijskom mikroskopijom je nađeno kako oba spoja djeluju razorno na citoskeletne mreže tubulina i aktina, a analizom Western blot je utvrđeno da spoj 1 djeluje i na smanjenje njihove ekspresije. Spoj 1 pokazao je jače djelovanje na citoskeletni sustav. Mjerenjem proizvodnje reaktivnih kisikovih vrsta (ROS) ustanovljen je jači antioksidativni efekt spoja 2. Zajednički mehanizam djelovanja nije nađen, usprkos mnogim sličnostima među spojevima. Ovim rezultatima djelomično su rasvijetljeni mehanizmi protutumorskog djelovanja cijanosupstituiranih heteroarila na stanice HeLa.
Abstract (english)
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.
Keywords
Keywords (english)
Languagecroatian
URN:NBNurn:nbn:hr:217:089026
Study programmeTitle: Molecular Biology
Study programme type: university
Study level: graduate
Academic / professional title: magistar/magistra molekularne biologije (magistar/magistra molekularne biologije)
Type of resourceText
File originBorn digital
Access conditionsAccess restricted to students and staff of home institution
Terms of useLicence In copyright icon
Created on2017-05-04 07:35:20