Page 85 - SDIR5 Abstract book 21 12 2021.

POSTER PRESENTATIONS

P45

Anticancer effects of sclareol and its derivatives in glioblastoma cells

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Ana Kostić , Ema Lupšić , Pavle Stojković , Miodrag Dragoj , Sofija Jovanović Stojanov , Nataša Terzić-
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Jovanović , Miroslav Novaković , Igor M. Opsenica and Milica Pešić
1 Institute for Biological Research “Siniša Stanković” - National Institute of Republic of Serbia, University of Belgrade,
Department of Neurobiology, Bulevar Despota Stefana 142, 11060 Belgrade, Serbia
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University of Belgrade-Faculty of Chemistry, P.O. Box 51, Studentski Trg 16, 11158 Belgrade, Serbia
3 Institute of Chemistry, Technology and Metallurgy, National Institute of Republic of Serbia, University of Belgrade,
Njegoševa 12, 11000 Belgrade, Serbia

Background: Glioblastoma is the most common, aggressive and lethal brain tumor in adults with high
proliferation rate, infiltrating nature and presence of multidrug resistance (MDR). Sclareol (SC) is a naturally
occurring labdane type diterpene, derived from Salvia sclarea. We examined cell growth inhibition effect
of SC and its derivatives (PAS and TNT groups of compounds) - hybrid (chimeric) molecules. Sclareol was
covalently bonded to [1,2,4]triazolo[1,5-a]pyrimidin-7-amine scaffold, and different diamines were used as
linkers. We also studied SC potential to reverse DOX resistance and its accumulation. The combination of
SC with DOX has been earlier described to potentiate DOX cytotoxicity if simultaneously delivered in
nanoparticles. Material and Methods: SC in combination with DOX as well as SC derivatives were tested on
human glioma cell line U87, and its MDR counterpart - U87-TxR. MTT assay was used to examine inhibition
of cell growth. Accumulation of DOX was measured by flow cytometry. Results: Thirteen out of nineteen
TNT derivatives and three out of six PAS derivatives showed stronger anti-glioma effect than SC.
Simultaneous treatment of SC with DOX demonstrated potential of SC to reverse DOX resistance. Even
more, SC significantly increased DOX accumulation in both glioblastoma cell lines. Conclusion: Results
obtained in this study showed a considerable synergy of SC and DOX in glioma cells. Better results observed
with SC derivatives make them good candidates for further testing.
Keywords: chemotherapy, doxorubicin, glioblastoma, MDR, sclareol
Acknowledgement: Ministry of Education, Science and Technological Development, Republic of Serbia (ref.
numbers 451-03-9/2021-14/200007, 451-03-9/2021-14/200168).

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