prikaz prve stranice dokumenta Azabicycloheptane-thiourea derivatives with potent cytotoxic effects on non-small cell lung cancer (NSCLC) cell lines
Embargo period 2026-09-25
master's thesis
Azabicycloheptane-thiourea derivatives with potent cytotoxic effects on non-small cell lung cancer (NSCLC) cell lines
2024. urn:nbn:hr:193:367933
Dobrović, Daria
University of Rijeka
Faculty of Biotechnology and Drug Development

Cite this document

Dobrović, D. (2024). Azabicycloheptane-thiourea derivatives with potent cytotoxic effects on non-small cell lung cancer (NSCLC) cell lines (Master's thesis). Rijeka: University of Rijeka. Retrieved from https://urn.nsk.hr/urn:nbn:hr:193:367933

Dobrović, Daria. "Azabicycloheptane-thiourea derivatives with potent cytotoxic effects on non-small cell lung cancer (NSCLC) cell lines." Master's thesis, University of Rijeka, 2024. https://urn.nsk.hr/urn:nbn:hr:193:367933

Dobrović, Daria. "Azabicycloheptane-thiourea derivatives with potent cytotoxic effects on non-small cell lung cancer (NSCLC) cell lines." Master's thesis, University of Rijeka, 2024. https://urn.nsk.hr/urn:nbn:hr:193:367933

Dobrović, D. (2024). 'Azabicycloheptane-thiourea derivatives with potent cytotoxic effects on non-small cell lung cancer (NSCLC) cell lines', Master's thesis, University of Rijeka, accessed 20 January 2025, https://urn.nsk.hr/urn:nbn:hr:193:367933

Dobrović D. Azabicycloheptane-thiourea derivatives with potent cytotoxic effects on non-small cell lung cancer (NSCLC) cell lines [Master's thesis]. Rijeka: University of Rijeka; 2024 [cited 2025 January 20] Available at: https://urn.nsk.hr/urn:nbn:hr:193:367933

D. Dobrović, "Azabicycloheptane-thiourea derivatives with potent cytotoxic effects on non-small cell lung cancer (NSCLC) cell lines", Master's thesis, University of Rijeka, Rijeka, 2024. Available at: https://urn.nsk.hr/urn:nbn:hr:193:367933

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Metadata
TitleAzabicycloheptane-thiourea derivatives with potent cytotoxic effects on non-small cell lung cancer (NSCLC) cell lines
Title (croatian)Azabicikloheptan-tiourea derivati s jakim citotoksičnim učinkom na stanične linije nemalih stanica raka pluća
AuthorDaria Dobrović
MentorJosé Padrón (mentor)
Committee memberDean Marković (predsjednik povjerenstva)
Committee memberDuško Čakara (član povjerenstva)
Committee memberStribor Marković (član povjerenstva)
Committee memberJosé Padrón (član povjerenstva)
GranterUniversity of Rijeka
(Faculty of Biotechnology and Drug Development)
Rijeka
Defense date and country2024-09-25, Croatia
Scientific / art field,
discipline and subdiscipline		BIOTECHNICAL SCIENCES
Biotechnology
Abstract
Cancer remains a leading cause of death worldwide, with lung cancer being the most prevalent and deadly. Key challenges in cancer therapy include molecular heterogeneity and drug resistance. Phenotypic drug discovery (PDD) approach was used to identify a subset of compounds from a small library of azabicycloheptane-thiourea derivatives, which exhibit significant antiproliferative effects in non-small cell lung cancer (NSCLC) cell lines. The primary objective of this study was to elucidate the mode of action of selected compounds, with a focus on identifying the type of cell death they induce. To accomplish this, live-cell imaging and experiments assessing potential mitochondrial, cytoskeletal, and DNA damage were conducted. Live-cell imaging revealed the presence of vacuoles emerging shortly before cell death, suggesting a link between vacuole formation and the compounds' cytotoxic effects. These vacuoles were found to be non-acidic and ruled out as autophagosomes. No mitochondrial or cytoskeletal damage was observed, while DNA damage was only detected after prolonged exposure. The findings suggest that these compounds induce a methuosis-like type of cell death in the SW1573 cell line. Methuosis is a non-apoptotic cell death pathway characterized by extreme vacuolization derived from macropinosomes. This research highlights the potential of non-apoptotic cell death pathways, like methuosis, as a novel approach to overcome drug resistance in cancer therapy.
Abstract (croatian)
Rak ostaje vodeći uzrok smrti u svijetu, pri čemu je rak pluća najčešći i najsmrtonosniji. Ključni izazovi u terapiji raka uključuju molekularnu heterogenost i otpornost na lijekove. Fenotipski pristup otkrivanju lijekova (PDD) korišten je za identifikaciju podskupa spojeva iz male biblioteke derivata azabicikloheptan-tiouree, koji pokazuju značajne antiproliferativne učinke na stanične linije nemalih stanica raka pluća (NSCLC). Primarni cilj ovog istraživanja bio je rasvijetliti mehanizam djelovanja odabranih spojeva, s posebnim naglaskom na identifikaciju vrste stanične smrti koju induciraju. Kako bi se to postiglo, provedeno je snimanje živih stanica te eksperimenti za procjenu potencijalnog oštećenja mitohondrija, citoskeleta i DNK. Snimanje živih stanica otkrilo je prisutnost vakuola koje se pojavljuju neposredno prije stanične smrti, što sugerira vezu između stvaranja vakuola i citotoksičnih učinaka spojeva. Ove vakuole su identificirane kao ne-kisele te su isključene kao autofagosomi. Oštećenje mitohondrija ili citoskeleta nije zabilježeno, dok je oštećenje DNK otkriveno tek nakon dugotrajne izloženosti. Rezultati sugeriraju da ovi spojevi induciraju metuozi-sličnu vrstu stanične smrti u staničnoj liniji SW1573. Metuoza je ne-apoptotski put stanične smrti karakteriziran ekstremnom vakuolizacijom koja potječe iz makropinosoma. Ovo istraživanje naglašava potencijal ne-apoptotskih puteva stanične smrti, poput metuoze, kao novog pristupa za prevladavanje otpornosti na lijekove u terapiji raka.
Keywords
Keywords (croatian)
Languagecroatian
URN:NBNurn:nbn:hr:193:367933
Study programmeTitle: Biotechnology in medicine
Study programme type: university
Study level: graduate
Academic / professional title: magistar/magistra biotehnologije u medicini (magistar/magistra biotehnologije u medicini)
Type of resourceText
File originBorn digital
Access conditionsEmbargoed access
Embargo expiration date: 2026-09-25
Terms of useLicence In copyright icon
Created on2024-09-26 09:00:52