Ruthenacarborane and Quinoline: A Promising Combination for the Treatment of Brain Tumors
2021
Authors:
Drača, DijanaMarković, Milan
Gozzi, Marta
Mijatović, Sanja
Maksimović-Ivanić, Danijela
Hey-Hawkins, Evamarie
Document Type:
Article (Published version)
Metadata
Show full item recordAbstract:
Gliomas and glioblastomas are very aggressive forms of brain tumors, prone to the devel opment of a multitude of resistance mechanisms to therapeutic treatments, including cytoprotective
autophagy. In this work, we investigated the role and mechanism of action of the combination of a
ruthenacarborane derivative with 8-hydroxyquinoline (8-HQ), linked via an ester bond (complex 2),
in rat astrocytoma C6 and human glioma U251 cells, in comparison with the two compounds alone,
i.e., the free carboxylic acid (complex 1) and 8-HQ, and their non-covalent combination ([1 + 8-HQ],
in 1:1 molar ratio). We found that only complex 2 was able to significantly affect cellular viability
in glioma U251 cells (IC50 11.4 µM) via inhibition of the autophagic machinery, most likely acting
at the early stages of the autophagic cascade. Contrary to 8-HQ alone, complex 2 was also able
to impair cellular viability under conditions of glucose deprivation. We thus suggest different
mechanisms of action of ruthenacarborane complex 2 than purely organic quinoline-based drugs,
making complex 2 a very attractive candidate for evading the known resistances of brain tumors to
chloroquine-based therapies.
Keywords:
ruthenacarborane; autophagy; glucose deprivation; gliomaSource:
Molecules, 2021, 26, 13, 3801-Funding / projects:
- DFG (HE 1376/38-1)
- 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)
DOI: 10.3390/molecules26133801
ISSN: 1420-3049
PubMed: 34206482