Sesquiterpene Lactones as Promising Anti-Glioblastoma Drug Candidates Exerting Complex Effects on Glioblastoma Cell Viability and Proneural–Mesenchymal Transition

Glioblastoma is one of the most aggressive brain cancers, characterized by active infiltrative growth and high resistance to radiotherapy and chemotherapy. Sesquiterpene triterpenoids (STLs) and their semi-synthetic analogs are considered as a promising source of novel anti-tumor agents due to their...

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Main Authors: Andrey V. Markov, Arseny D. Moralev, Kirill V. Odarenko
Format: Article
Language:English
Published: MDPI AG 2025-01-01
Series:Biomedicines
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Online Access:https://www.mdpi.com/2227-9059/13/1/133
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author Andrey V. Markov
Arseny D. Moralev
Kirill V. Odarenko
author_facet Andrey V. Markov
Arseny D. Moralev
Kirill V. Odarenko
author_sort Andrey V. Markov
collection DOAJ
description Glioblastoma is one of the most aggressive brain cancers, characterized by active infiltrative growth and high resistance to radiotherapy and chemotherapy. Sesquiterpene triterpenoids (STLs) and their semi-synthetic analogs are considered as a promising source of novel anti-tumor agents due to their low systemic toxicity and multi-target pharmacological effects on key processes associated with tumor progression. The current review aims to systematize the knowledge on the anti-glioblastoma potential of STLs accumulated over the last decade and to identify key processes in glioblastoma cells that are most susceptible to the action of STLs. An analysis of published data clearly demonstrated that STLs, which can successfully cross the blood–brain barrier, exert a complex inhibitory effect on glioblastoma cells through the induction of the “mitochondrial dysfunction–oxidative stress–apoptosis” axis, the inhibition of glucose metabolism and cell cycle phase transition, and the suppression of glioblastoma cell motility and invasion through the blockade of proneural–mesenchymal transition. Taken together, this review highlights the promising anti-glioblastoma potential of STLs, which are not only able to induce glioblastoma cell death, but also effectively affect their diffusive spread, and suggests the possible directions for further investigation of STLs in the context of glioblastoma to better understand their mechanism of action.
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spelling doaj-art-33a34b71a3054bb3a368d8521f7d38672025-01-24T13:24:07ZengMDPI AGBiomedicines2227-90592025-01-0113113310.3390/biomedicines13010133Sesquiterpene Lactones as Promising Anti-Glioblastoma Drug Candidates Exerting Complex Effects on Glioblastoma Cell Viability and Proneural–Mesenchymal TransitionAndrey V. Markov0Arseny D. Moralev1Kirill V. Odarenko2Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, Lavrent’ev Avenue 8, 630090 Novosibirsk, RussiaInstitute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, Lavrent’ev Avenue 8, 630090 Novosibirsk, RussiaInstitute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, Lavrent’ev Avenue 8, 630090 Novosibirsk, RussiaGlioblastoma is one of the most aggressive brain cancers, characterized by active infiltrative growth and high resistance to radiotherapy and chemotherapy. Sesquiterpene triterpenoids (STLs) and their semi-synthetic analogs are considered as a promising source of novel anti-tumor agents due to their low systemic toxicity and multi-target pharmacological effects on key processes associated with tumor progression. The current review aims to systematize the knowledge on the anti-glioblastoma potential of STLs accumulated over the last decade and to identify key processes in glioblastoma cells that are most susceptible to the action of STLs. An analysis of published data clearly demonstrated that STLs, which can successfully cross the blood–brain barrier, exert a complex inhibitory effect on glioblastoma cells through the induction of the “mitochondrial dysfunction–oxidative stress–apoptosis” axis, the inhibition of glucose metabolism and cell cycle phase transition, and the suppression of glioblastoma cell motility and invasion through the blockade of proneural–mesenchymal transition. Taken together, this review highlights the promising anti-glioblastoma potential of STLs, which are not only able to induce glioblastoma cell death, but also effectively affect their diffusive spread, and suggests the possible directions for further investigation of STLs in the context of glioblastoma to better understand their mechanism of action.https://www.mdpi.com/2227-9059/13/1/133brain tumorterpenestumor cell deathmitochondrial dysfunctionepithelial–mesenchymal transitionglial–mesenchymal transition
spellingShingle Andrey V. Markov
Arseny D. Moralev
Kirill V. Odarenko
Sesquiterpene Lactones as Promising Anti-Glioblastoma Drug Candidates Exerting Complex Effects on Glioblastoma Cell Viability and Proneural–Mesenchymal Transition
Biomedicines
brain tumor
terpenes
tumor cell death
mitochondrial dysfunction
epithelial–mesenchymal transition
glial–mesenchymal transition
title Sesquiterpene Lactones as Promising Anti-Glioblastoma Drug Candidates Exerting Complex Effects on Glioblastoma Cell Viability and Proneural–Mesenchymal Transition
title_full Sesquiterpene Lactones as Promising Anti-Glioblastoma Drug Candidates Exerting Complex Effects on Glioblastoma Cell Viability and Proneural–Mesenchymal Transition
title_fullStr Sesquiterpene Lactones as Promising Anti-Glioblastoma Drug Candidates Exerting Complex Effects on Glioblastoma Cell Viability and Proneural–Mesenchymal Transition
title_full_unstemmed Sesquiterpene Lactones as Promising Anti-Glioblastoma Drug Candidates Exerting Complex Effects on Glioblastoma Cell Viability and Proneural–Mesenchymal Transition
title_short Sesquiterpene Lactones as Promising Anti-Glioblastoma Drug Candidates Exerting Complex Effects on Glioblastoma Cell Viability and Proneural–Mesenchymal Transition
title_sort sesquiterpene lactones as promising anti glioblastoma drug candidates exerting complex effects on glioblastoma cell viability and proneural mesenchymal transition
topic brain tumor
terpenes
tumor cell death
mitochondrial dysfunction
epithelial–mesenchymal transition
glial–mesenchymal transition
url https://www.mdpi.com/2227-9059/13/1/133
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