Anticancer effects of sclareol and its derivatives in glioblastoma cells
2021
Аутори:
Stepanović, AnaLupšić, Ema
Stojković, Pavle
Dragoj, Miodrag
Jovanović Stojanov, Sofija
Terzić- Jovanović, Nataša
Novaković, Miroslav
Opsenica, Igor M.
Pešić, Milica
Остала ауторства
Đorđić Crnogorac, MarijaNedeljković, Milica
Тип документа:
Конференцијски прилог (Објављена верзија)
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© 2021 by the Serbian Association for Cancer Research
Метаподаци
Приказ свих података о документуАпстракт:
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.
Кључне речи:
chemotherapy; doxorubicin; glioblastoma; MDR; sclareolФинансирање / пројекти:
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200007 (Универзитет у Београду, Институт за биолошка истраживања 'Синиша Станковић') (RS-MESTD-inst-2020-200007)
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200168 (Универзитет у Београду, Хемијски факултет) (RS-MESTD-inst-2020-200168)
У:
- Đorđić Crnogorac M, Nedeljković M, editors. Abstract book: The fifth congress of the Serbian association for cancer research:“Translational potential of cancer research in Serbia“; 2021 Dec 3; Virtual. Belgrade: Serbian Association for Cancer Research; 2021. p. 72.