Utjecaj duljine izloženosti oksidacijskom stresu na modulaciju antioksidacijskog odgovora i metabolizma u stanica tumora dojke

master's thesis

• Title (english): Influence of the oxidative stress duration on the modulation of antioxidative response and metabolism in breast cancer cells
• Author: Monika Mlinarić
• Mentor: Lidija Milković (mentor)
• Mentor: Nada Oršolić (sumentor)
• Committee member: Nada Oršolić (predsjednik povjerenstva)
• Committee member: Biljana Balen (član povjerenstva)
• Committee member: Romana Gračan (član povjerenstva)
• Committee member: Maja Matulić (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2021-01-25, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology

Abstract

Reaktivne kisikove vrste (ROS, engl. Reactive oxygen species) su nužne za funkcioniranje fizioloških procesa u stanicama, no mogu doprinijeti i razvoju bolesti kao što su tumori. Nepoželjno djelovanje ROS-a nastupa uslijed njihove nedostatne eliminacije antioksidansima tijekom oksidacijskog stresa (OS). Osim što je OS uključen u sve faze nastanka i razvoja tumora, u samih je tumorskih stanica pokazana povećana razina ROS-a u odnosu na zdrave, karakteristika koju iskorištava većina konvencionalne terapije bazirane na selektivnom povećanju ROS-a. Kako ne bi došlo do smrti zbog oksidacijskih oštećenja, tumorske stanice često imaju i pojačane antioksidacijske mehanizme zaštite te mijenjaju svoj metabolizam sukladno potrebama rasta. Heterogenost samih tumora doprinosi različitim odgovorima na terapiju. Ovim je istraživanjem ispitivan utjecaj duljine izloženosti različitim koncentracijama vodikovog peroksida na trima tipovima staničnih linija tumora dojke: MCF-7 (hormonski pozitivne), SkBr-3 (HER2 pozitivne) i SUM 159 (trostruko negativne). Proučavana je stanična vijabilnost, razina endogenih ROS-a, te ekspresija proteina i aktivnost glutationa i katalaze radi otkrivanja potencijalnih razlika u antioksidacijskoj zaštiti i aktivaciji metabolizma. Rezultati ukazuju na razlike u odgovoru staničnih linija u ovisnosti o koncentraciji i duljini izloženosti vodikovom peroksidu. Stanična linija MCF-7 se pokazala najmanje osjetljivom, dok je SUM 159 bila najosjetljivija.

Abstract (english)

Although necessary for physiological cell functions, reactive oxygen species (ROS) can also contribute to the development of diseases such as tumors. Their detrimental effect is associated with their insufficient elimination by antioxidants during oxidative stress (OS). In addition to OS being involved in all stages of tumor development and progression, tumor cells have been shown to have increased levels of ROS compared to healthy ones, a feature exploited by most conventional therapies based on selective ROS augmentation. To avoid oxidative damage-induced death, tumor cells often enhance antioxidant defense mechanisms and reprogram their metabolism to boost tumor growth. The heterogeneity of the tumors contributes to different responses to therapy. This study aimed to investigate the effect of length of exposure to different concentrations of hydrogen peroxide on three breast cancer cell lines: MCF-7 (hormone positive), SkBr-3 (HER2 positive), and SUM 159 (triple-negative). Cell viability, endogenous levels of ROS, protein expression, and glutathione and catalase activity were studied to explore potential differences in antioxidative capacity and metabolic activation. The results indicate cell line-dependent response to concentration and length of exposure to hydrogen peroxide. The MCF-7 cell line was the least sensitive, while the SUM 159 was the most sensitive.

• Keywords: oksidacijski stres; vodikov peroksid; stanične linije tumora dojke; antioksidacijska obrana; signalni put NRF2; metaboličko reprogramiranje
• Keywords (english): oxidative stress; hydrogen peroxide; breast cancer cell lines; antioxidative defense; the NRF2 signaling pathway; metabolic reprogramming
• Language: croatian
• URN:NBN: urn:nbn:hr:217:857205
• Study programme: Title: Experimental Biology; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra eksperimentalne biologije (magistar/magistra eksperimentalne biologije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access; Embargo expiration date: 2022-01-25
• Created on: 2021-02-12 13:57:19