TY  - CONF
AU  - Lupšić, Ema
AU  - Stepanović, Ana
AU  - Stojković, Pavle
AU  - Terzić-Jpvanović, Nataša
AU  - Novaković, Miroslav
AU  - Nedialkov, Paraskev
AU  - Trendafilova, Antoaneta
AU  - Opsenica, Igor M.
AU  - Pešić, Milica
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5928
AB  - Background: Glioblastoma is a highly aggressive and resistant brain tumor. P-glycoprotein
(P-gp) constitutes the blood-brain barrier and is expressed on the cell membrane of multidrugresistant (MDR) glioblastoma cells. Our objective was to investigate the anti-glioblastoma
effects of sclareol (SCL), a natural diterpene alcohol, and its two derivatives (11c and 12l).
Methods: Our cellular model included human glioblastoma U87 cell line without P-gp
expression, its MDR counterpart U87-TxR with P-gp expression, and normal lung fibroblasts
MRC-5. Cytotoxic effects were examined by MTT. P-gp function, cell cycle disturbance,
time-dependent cell death induction, the level of reactive oxygen and nitrogen species, and
changes in the mitochondrial membrane potential were studied by flow cytometry. Results:
SCL and its derivatives evaded the MDR in glioblastoma cells, showing lower IC50 values in
U87-TxR than in U87, referred to as collateral sensitivity. Both derivatives were more potent
than SCL, while 12l was active in the nanomolar range. 11c and 12l displayed greater
selectivity towards glioblastoma cells compared to SCL. All compounds significantly
disturbed the cell cycle and induced cell death: SCL - late apoptosis and necrosis, 11c - only
early apoptosis, and 12l - early and late apoptosis. SCL and its derivatives acted as
antioxidants, while 11c and 12l decreased mitochondrial membrane potential. Conclusion:
SCL derivatives were more potent than SCL. The observed collateral sensitivity in
glioblastoma cells can be explained by oxidative stress modulation because although resistant
due to P-gp expression, U87-TxR cells are more susceptible to changes in oxidative status
than U87 cells.
PB  - Belgrade: Serbian Neuroscience Society
C3  - Book of abstracts: 8th Congress of Serbian neuroscience society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia
T1  - Evading multidrug resistance in glioblastoma with natural compound sclareol and its novel derivatives
SP  - 72
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5928
ER  - 

@conference{
author = "Lupšić, Ema and Stepanović, Ana and Stojković, Pavle and Terzić-Jpvanović, Nataša and Novaković, Miroslav and Nedialkov, Paraskev and Trendafilova, Antoaneta and Opsenica, Igor M. and Pešić, Milica",
year = "2023",
abstract = "Background: Glioblastoma is a highly aggressive and resistant brain tumor. P-glycoprotein
(P-gp) constitutes the blood-brain barrier and is expressed on the cell membrane of multidrugresistant (MDR) glioblastoma cells. Our objective was to investigate the anti-glioblastoma
effects of sclareol (SCL), a natural diterpene alcohol, and its two derivatives (11c and 12l).
Methods: Our cellular model included human glioblastoma U87 cell line without P-gp
expression, its MDR counterpart U87-TxR with P-gp expression, and normal lung fibroblasts
MRC-5. Cytotoxic effects were examined by MTT. P-gp function, cell cycle disturbance,
time-dependent cell death induction, the level of reactive oxygen and nitrogen species, and
changes in the mitochondrial membrane potential were studied by flow cytometry. Results:
SCL and its derivatives evaded the MDR in glioblastoma cells, showing lower IC50 values in
U87-TxR than in U87, referred to as collateral sensitivity. Both derivatives were more potent
than SCL, while 12l was active in the nanomolar range. 11c and 12l displayed greater
selectivity towards glioblastoma cells compared to SCL. All compounds significantly
disturbed the cell cycle and induced cell death: SCL - late apoptosis and necrosis, 11c - only
early apoptosis, and 12l - early and late apoptosis. SCL and its derivatives acted as
antioxidants, while 11c and 12l decreased mitochondrial membrane potential. Conclusion:
SCL derivatives were more potent than SCL. The observed collateral sensitivity in
glioblastoma cells can be explained by oxidative stress modulation because although resistant
due to P-gp expression, U87-TxR cells are more susceptible to changes in oxidative status
than U87 cells.",
publisher = "Belgrade: Serbian Neuroscience Society",
journal = "Book of abstracts: 8th Congress of Serbian neuroscience society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia",
title = "Evading multidrug resistance in glioblastoma with natural compound sclareol and its novel derivatives",
pages = "72",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5928"
}

Lupšić, E., Stepanović, A., Stojković, P., Terzić-Jpvanović, N., Novaković, M., Nedialkov, P., Trendafilova, A., Opsenica, I. M.,& Pešić, M.. (2023). Evading multidrug resistance in glioblastoma with natural compound sclareol and its novel derivatives. in Book of abstracts: 8th Congress of Serbian neuroscience society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia
Belgrade: Serbian Neuroscience Society., 72.
https://hdl.handle.net/21.15107/rcub_ibiss_5928

Lupšić E, Stepanović A, Stojković P, Terzić-Jpvanović N, Novaković M, Nedialkov P, Trendafilova A, Opsenica IM, Pešić M. Evading multidrug resistance in glioblastoma with natural compound sclareol and its novel derivatives. in Book of abstracts: 8th Congress of Serbian neuroscience society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia. 2023;:72.
https://hdl.handle.net/21.15107/rcub_ibiss_5928 .

Lupšić, Ema, Stepanović, Ana, Stojković, Pavle, Terzić-Jpvanović, Nataša, Novaković, Miroslav, Nedialkov, Paraskev, Trendafilova, Antoaneta, Opsenica, Igor M., Pešić, Milica, "Evading multidrug resistance in glioblastoma with natural compound sclareol and its novel derivatives" in Book of abstracts: 8th Congress of Serbian neuroscience society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia (2023):72,
https://hdl.handle.net/21.15107/rcub_ibiss_5928 .