New anti-glioblastoma strategy with natural compounds sclareol and doxorubicin
2023
Authors:
Stepanović, AnaLupšić, Ema
Dinić, Jelena
Podolski-Renić, Ana
Pajović, Milica
Jovanović Stojanov, Sofija
Dragoj, Miodrag
Terzić Jovanović, Nataša
Opsenica, Igor
Pešić, Milica
Contributors
Kanazir, SelmaSavić, Danijela
Document Type:
Conference object (Published version)
,
© 2023 by Serbian Neuroscience Society and associates
Metadata
Show full item recordAbstract:
Background: Doxorubicin (DOX) has been very effective against glioblastoma in
vitro. Its application in vivo is hampered because it cannot pass the blood–brain
barrier (BBB). Significant research efforts are invested to overcome this limitation.
Sclareol (SC) is an aromatic compound naturally found in clary sage. The
combination of SC and DOX showed promising effects in different tumor types in
vitro and in vivo. Therefore, we tested their combination and innovative hybrid
molecules (SC:DOX) on glioblastoma cells with the expression of P-glycoprotein, a
major component of BBB and cancer multidrug resistance marker. Methods:
Cytotoxicity and selectivity towards glioblastoma cells of SC, DOX, their
combination, and SC:DOX were examined by MTT assay. The effect of SC on DOX
accumulation was determined by flow cytometry. We also studied SC:DOX
accumulation, cellular uptake, localization imaging, and DNA damage induction.
Results: The effects of simultaneous SC and DOX treatments demonstrated the
considerable potential of SC to reverse DOX resistance in glioblastoma cells and
increase DOX accumulation. SC:DOX hybrids, named CON1 and CON2 were less
cytotoxic than DOX, but with reduced resistance and increased selectivity towards
glioblastoma cells. Cellular uptake of CON1 and CON2 was increased in glioblastoma
cells compared to DOX. Perinuclear localization of CON1 and CON2 vs. nuclear
localization of DOX as well as no DNA damaging effects suggest a different
mechanism of action for SC:DOX. Conclusion: The combination of SC and DOX, and
their innovative hybrids, could be considered a promising strategy that can overcome
the limitations of DOX application in glioblastoma.
Funding / projects:
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200007 (University of Belgrade, Institute for Biological Research 'Siniša Stanković') (RS-MESTD-inst-2020-200007)
In:
- Kanazir S, Savić D, editors. Book of abstracts: 8th Congress of Serbian neuroscience society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia. Belgrade : Serbian Neuroscience Society; 2023. p. 71.