Metaboličke promjene u matičnim stanicama sarkoma uzrokovane dehidro-L-askorbinskom kiselinom

master's thesis

• Title (english): Metabolic changes in sarcoma stem cells induced by dehydro-L-ascorbic acid
• Author: Zara Škibola
• Mentor: Inga Urlić (mentor)
• Mentor: Maja Ledinski (komentor)
• Committee member: Inga Urlić (predsjednik povjerenstva)
• Committee member: Maja Matulić (član povjerenstva)
• Committee member: Nada Oršolić (član povjerenstva)
• Committee member: Vesna Benković (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2023-01-31, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology

Abstract

Matične stanice tumora posebna su grupa tumorskih stanica sa sposobnošću samoobnavljanja i
smatra se da su ključne za inicijaciju i rast tumora. Često su otporne na konvencionalne terapije
što predstavlja veliki problem u liječenju. Smatra se da vitamin C ima različite antitumorske
mehanizme koji se razlikuju ovisno o vrsti tumora. Vitamin C osim što narušava redoks stanje
u stanicama i uzrokuje oksidacijski stres također mijenja i metabolički profil stanice. U ovom
radu se istraživao učinak oksidiranog oblika vitamina C, dehidroaskorbinske kiseline (DHA),
na matične stanice sarkoma. Milimolarne koncentracije DHA u mediju sa i bez bazičnog FGFa smanjile su vijabilnost svih tretiranih staničnih linija. Također je pokazano kako tretmani s
DHA mijenjaju ekspresiju gena važnih za glikolizu i oksidativnu fosforilaciju. Ekspresija
gliceraldehid-3-fosfat dehidrogenaze je gledana i na razini proteina gdje je također zabilježeno
da dolazi do promjena. Pošto su sarkomi vrlo heterogena skupina tumora, tri vrste matičnih
stanica pokazale su različite odgovore na tretman DHA. Općenito, matične stanice
hondrosarkoma i osteosarkoma su pokazale bolji odgovor od stanica rabdomiosarkoma. DHA
je pokazala potencijal kao modulator metabolizma matičnih stanica sarkoma, ali za daljnji
razvoj kao antitumorske terapije svakako treba uzeti u obzir specifičnu pozadinu tumora.

Abstract (english)

Cancer stem cells are a subpopulation of tumor cells with the ability of self-renewal and are
thought to drive tumor initiation and growth. Cancer stem cells are resistant to conventional
therapy which poses major problem in treatment. Vitamin C is thought to have different antitumor mechanisms that differ depending on the type of tumor. Apart from disrupting the redox
state in cells and causing oxidative stress, vitamin C also changes the metabolic profile of the
cell. In this work, the effect of the oxidized form of vitamin C, dehydroascorbic acid (DHA),
on three sarcoma stem cell types was investigated. Millimolar concentrations of DHA in
medium with and without basic FGF decreased the viability of all treated cell lines. This work
also demonstrated that treatments with DHA alter the expression of genes important for
glycolysis and oxidative phosphorylation. Effects of DHA treatment on change of
glyceraldehyde-3-phosphate dehydrogenase protein expression were also shown. However,
sarcomas are a very heterogeneous group of tumors, so three types of stem cells showed
different responses to DHA treatment. General response to treatment was more positive in
chondrosarcoma and osteosarcoma stem cells than in rhabdomyosarcoma stem cells. DHA has
shown potential as a modulator of sarcoma stem cell metabolism, but for further development
as an anti-tumor therapy, the specific background of the tumor must be considered.

• Keywords: metabolizam sarkoma; GAPDH; PGC-1α; vitamin C
• Keywords (english): sarcoma metabolism; GAPDH; PGC-1α; vitamin C
• Language: croatian
• URN:NBN: urn:nbn:hr:217:005190
• 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; Embargo expiration date: 2024-01-31
• Created on: 2023-02-09 12:14:37