Utjecaj okratoksina A i patulina na metabolizam stanica raka dojke čovjeka

master's thesis

• Title (english): The impact of ochratoxin A and patulin on the metabolis of human breast cancer cells
• Author: Katarina Soža
• Mentor: Morana Jaganjac (mentor)
• Mentor: Nada Oršolić (komentor)
• Committee member: Nada Oršolić (predsjednik povjerenstva)
• Committee member: Maja Matulić (član povjerenstva)
• Committee member: Romana Gračan (član povjerenstva)
• Committee member: Ivana Šola (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2023-12-19, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology

Abstract

Mikotoksini, sekundarni metaboliti plijesni, često su prisutni u hrani biljnog i životinjskog podrijetla. Izloženost mikotoksinima predstavlja globalni problem te ovisno o trajanju izloženosti i koncentraciji pojedinog mikotoksina mogu imati različite negativne učinke po zdravlje čovjeka, uključujući i razvoj raka. Učestalost okratoksina A (OTA) i patulina (PAT) iznimno je visoka u hrani, a pretpostavke su da OTA i PAT utječu na staničnu redoks homeostazu te dovode do metaboličkog reprogramiranja stanica, što spada u neka od osnovnih obilježja raka. Ovim istraživanjem određen je učinak biološki relevantnih koncentracija OTA i PAT na staničnu redoks homeostazu te promjene u metabolizmu staničnih linija raka dojke čovjeka MCF7, koje imaju receptore steroidnih hormona i SUM159, koje nemaju receptore estrogena i progesterona te receptor humanog epidermalnog čimbenika rasta 2. Stanična redoks homeostaza praćena je stvaranjem reaktivnih kisikovih vrsta te određivanjem aktivnosti staničnog antioksidansa katalaze. Praćenjem migracije stanica određen je mogući učinak na metastaziranje stanica raka dojke. Mjerenjem potrošnje kisika određen je učinak na funkciju i učinkovitost mitohondrija, a promjene inducirane izlaganjem stanica OTA-u i PAT-u na metabolički profil određene su masenom spektrometrijom. Ovo istraživanje pokazalo je da OTA i PAT dovode do promjena u metabolizmu stanica raka dojke pokazujući uključenost oksidacijskog stresa kao mogućeg mehanizma toksičnosti koji može dovesti do progresije ove bolesti.

Abstract (english)

Mycotoxins, secondary metabolites of molds, are often found in foods of plant and animal origin. Exposure to mycotoxins is a worldwide problem and their adverse effects on human health, including the development of cancer, can vary depending on the duration of exposure and the concentration of the individual mycotoxin. The incidence of ochratoxin A (OTA) and patulin (PAT) in food is extremely high, and OTA and PAT are thought to disrupt cellular redox homeostasis and lead to metabolic reprogramming of cells, which are among the hallmarks of cancer. In this study, the effect of biologically relevant concentrations of OTA and PAT on cellular redox homeostasis and metabolic changes in the human breast cancer cell lines MCF7 (expressing steroid receptors) and SUM159 (without expression of human epidermal growth factor receptor 2, estrogen and progesterone receptors) was investigated. The influence on cellular redox homeostasis is determined by monitoring the formation of reactive oxygen species and by determining the activity of the cellular antioxidant catalase. The metastatic potential of breast cancer cells was determined by studying cell migration. Measurements of oxygen consumption were used to assess the impact on mitochondrial function and efficiency, while mass spectrometry was used to identify the changes in metabolic profile induced by OTA and PAT. The results of this study show that OTA and PAT alter the metabolism of breast cancer cells, indicating the potential role of oxidative stress as a mechanism that may promote tumorigenesis.

• Keywords: okratoksin A; patulin; rak dojke; oksidacijski stres; metabolizam
• Keywords (english): o chratoxin A; patulin; breast cancer; oxidat ive stress; metaboli s m
• Language: croatian
• URN:NBN: urn:nbn:hr:217:313542
• Study programme: Title: Experimental Biology-University graduate programme; Study programme type: university; Study level: graduate; Academic / professional title: sveučilišni/a magistar/magistra eksperimentalne biologije (sveučilišni/a magistar/magistra eksperimentalne biologije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Embargoed access; Embargo expiration date: 2025-12-19
• Created on: 2024-01-11 11:02:55