Antitumor Effect of Traditional Drugs for Neurological Disorders: Preliminary Studies in Neural Tumor Cell Lines
MetadataShow full item record
AuthorDoello, Kevin; Mesas Hernández, Cristina; Quiñonero Muñoz, Francisco José; Rama, Ana Rosa; Vélez Fernández, María Celia; Perazzoli, Gloria; Ortiz Quesada, Raúl
Richard Kostrzewa Editor Neurotoxicity Research/Springer nature
GlioblastomaLevomepromazineHaloperidolLacosamideValproic acidLevetiracetamGlatiramer acetateFingolimodBiperidenDextromethorphan
Doello, K., Mesas, C., Quiñonero, F., Rama, A. R., Vélez, C., Perazzoli, G., & Ortiz, R. (2022). Antitumor Effect of Traditional Drugs for Neurological Disorders: Preliminary Studies in Neural Tumor Cell Lines. Neurotoxicity research, 10.1007/s12640-022-00606-3.
SponsorshipFunding for open access charge: Universidad de Granada / CBUA. This work was supported by the Project Innbio INB-009 (Granada University and ibs. GRANADA) and by the CTS-107 Group of the Junta de Andalucía (Spain).
Glioblastoma multiforme is the most common malignant primary brain tumor in adults. Despite new treatments developed including immunomodulation using vaccines and cell therapies, mortality remains high due to the resistance mechanisms presented by these tumor cells and the function of the blood–brain barrier that prevents the entry of most drugs. In this context of searching for new glioblastoma therapies, the study of the existing drugs to treat neurological disorder is gaining great relevance. The aim of this study was to determine, through a preliminary in vitro study on human glioblastoma (A172, LN229), anaplastic glioma (SF268) and neuroblastoma (SK-N-SH) cell lines, the possible antitumor activity of the active principles of several drugs (levomepromazine, haloperidol, lacosamide, valproic acid, levetiracetam, glatiramer acetate, fingolimod, biperiden and dextromethorphan) with the ability to cross the blood–brain barrier and that are commonly used in neurological disorders. Results showed that levetiracetam, valproic acid, and haloperidol were able to induce a relevant synergistic antitumor effect when associated with the chemotherapy currently used in clinic (temozolomide). Regarding the mechanism of action, haloperidol, valproic acid and levomepromazine caused cell death by apoptosis, while biperiden and dextromethorphan induced autophagy. Fingolimod appeared to have anoikis-related cell death. Thus, the assayed drugs which are able to cross the blood–brain barrier could represent a possibility to improve the treatment of neural tumors, though future in vivo studies and clinical trials will be necessary to validate it.