Učinak novosintetiziranih policikličkih i makrocikličkih spojeva na tumorske i tumorske matične stanice čovjeka

doctoral thesis

• Title (english): The effect of various polycyclic and macrocyclic compounds on human cancer and cancer stem cells
• Author: Lidija Uzelac
• Mentor: Marijeta Kralj (mentor)
• Committee member: Maja Matulić (član povjerenstva)
• Committee member: Maja Herak Bosnar (član povjerenstva)
• Committee member: Nikola Basarić (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2017-01-30, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology
• Universal decimal classification (UDC): 57 - Biological sciences. Physical anthropology. Biodiversity

Abstract

Ciljano uništavanje tumorskih matičnih stanica (TMS), za razliku od neselektivnog uništavanja tumorskih stanica, nova je strategija u liječenju raka. TMS su malobrojne populacije stanica unutar tumora koje imaju svojstvo samoobnavljanja i propagiranja u različite linije tumorskih stanica, jako su invazivne i izrazito neosjetljive na terapiju. U ovom smo radu ispitivali potencijalno protutumorsko djelovanje nekoliko skupina spojeva (makrocikličih krunastih etera i policikličkih derivata fenola), sintetiziranih na Institutu Ruđer Bošković, na tumorske stanične linije in vitro (HCT116, MCF-7, H460 i SUM 159) i/ili njihovo selektivno djelovanje na modelu HMLEshEcad, koja pokazuje karakteristike TMS i kontrolnoj liniji HMLEshGFP. Ispitali smo mogućnost fotoaktivacije policikličkih derivata fenola u reaktivne kinon-metide ili kisikove radikale koji alkiliraju makromolekule, odnosno izazivaju oksidativni stres. Najznačajniji učinak fotoaktivacije pokazuje nekoliko derivata antracena. Također isti spojevi pokazali su i selektivno djelovanje na modelu TMS. Ovo je istraživanje podloga za razvoj fototerapije, dok se mehanizam selektivnosti na TMS, temeljenoj na aktivaciji oksidativnog stresa, treba dodatno istražiti.

Abstract (english)

Targeting cancer stem cells (CSC), rather than cancer cells in general, is a novel and highly promising strategy for cancer treatment. CSC are cells within a tumor that possess the capacity to self-renew, propagate into the heterogeneous lineages of cancerous cells and that show an increased resistance to therapy. The objective of the proposed research is to test anticancer potential of macrocyclic compounds and polycyclic derivatives of phenols. Their activity was tested on a panel of human tumor cell lines (HCT116, MCF-7, H460 i SUM 159), as well as on a unique transgenic CSC model (HMLEshEcad/HMLEshGFP). We also investigated phenol derivatives to form quinone methides upon photochemical excitation and test their ability to alkylate macromolecules, or induce oxidative stress. The most intriguing activity and selectivity towards CSC cell model was demonstrated by several anthracenes. This study forms basis for further research on cancer phototherapy, as well as for elucidation of CSC selectivity based on oxidative stress activation.

• Keywords: protutumorska terapija; makrociklički spojevi; policiklički spojevi; krunasti eteri; kinon-metidi; tumorske matične stanice; fotokemoterapija
• Keywords (english): antitumor therapy; macrocyclic compounds; polycyclic compounds; crown ethers; quinone methides; cancer stem cells; photodynamic therapy
• Language: croatian
• URN:NBN: urn:nbn:hr:217:400164
• Study programme: Title: Biology; Study programme type: university; Study level: postgraduate; Academic / professional title: doktor/doktorica znanosti, područje prirodnih znanosti, polje biologija (doktor/doktorica znanosti, područje prirodnih znanosti, polje biologija)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Closed access
• Created on: 2017-02-08 12:59:29