Mehanizam djelovanja krunastog etera 613 na stanične linije dojke

master's thesis

• Title (english): Mechanism of action of crown ether compound 613 in breast cell lines
• Author: Jelena Gabrilo
• Mentor: Katja Ester (mentor)
• Mentor: Inga Marijanović (mentor)
• Committee member: Inga Marijanović (predsjednik povjerenstva)
• Committee member: Nada Oršolić (član povjerenstva)
• Committee member: Martina Šeruga Musić (član povjerenstva)
• Committee member: Maja Matulić (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2018-02-22, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology

Abstract

Prijašnja istraţivanja su pokazala kako krunasti eter 613 ima inhibitorni učinak na rast nekoliko tumorskih staničnih linija te da bi, s obzirom na strukturu, mogao djelovati kao mobilni nosač za ione natrija i kalija. Stoga se u sklopu ovog rada ispitivalo kako krunasti eter 613 djeluje na stanične linije tumora dojke i tumorske matične stanice dojke. Korištenjem anionske boje DiBAC4(3) utvrĎeno je da spoj značajno modulira membranski potencijal navedenih stanica, odnosno depolarizira ih. Testom MTT je pokazan i njegov antiproliferativni učinak na svim ispitivanim staničnim linijama. Kako bi se odredilo inducira li krunasti eter 613 apoptozu ili stanice umiru nekrozom, proveden je test Annexin V-FITC. Dobiveni rezultati upućuju na zaključak da je depolarizacija stanične membrane uzrokovana poremećajem homeostaze Na+, što izaziva stres za stanice na više razina te u konačnici uzrokuje smrt stanica. Ovi rezultati ukazuju na nove smjernice u istraţivanjima i primjeni krunastih etera u terapiji tumora.

Abstract (english)

Previous research has shown that crown ether compound 613 has an growth-inhibitory effect in different tumor cell lines. Considering its structure, it could act as a potassium and sodium ionophore. In this graduation thesis we tested its mechanism of action in breast tumor cell lines and breast cancer stem cell model. It was shown that the compound modulates cell membrane potential significantly, i.e. depolarizes cells. This was estimated using anionic dye DiBAC4(3). Its antiproliferative effect in tested cell lines was determined by the MTT assay. Annexin V-FITC test was performed in order to determine if cells die by apoptosis or necrosis. Our results indicate that cell membrane depolarization caused by disruption of sodium ion homeostasis leads to cellular stress and cell death eventually. These results give new directions in research and application of crown ethers in cancer therapy.

• Keywords: krunasti eter; tumor dojke; membranski potencijal; stanična smrt; ionofor
• Keywords (english): crown ether; breast cancer; membrane potential; cell death; ionophore
• Language: croatian
• URN:NBN: urn:nbn:hr:217:596076
• Study programme: Title: Molecular Biology; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra molekularne biologije (magistar/magistra molekularne biologije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2018-03-14 11:51:02