Deglucohellebrin: A Potent Agent for Glioblastoma Treatment

Evrysthenis Vartholomatos; George A Alexiou; Georgios S Markopoulos; Diamanto Lazari; Olga Tsiftsoglou; Ieremias Chousidis; Ioannis Leonardos; Athanasios P Kyritsis

doi:10.2174/1871520619666191121110848

Deglucohellebrin: A Potent Agent for Glioblastoma Treatment

Anticancer Agents Med Chem. 2020;20(1):103-110. doi: 10.2174/1871520619666191121110848.

Authors

Evrysthenis Vartholomatos¹, George A Alexiou¹, Georgios S Markopoulos², Diamanto Lazari³, Olga Tsiftsoglou³, Ieremias Chousidis⁴, Ioannis Leonardos⁴, Athanasios P Kyritsis¹

Affiliations

¹ Neurosurgical Institute, Medical School, University of Ioannina, Ioannina, Greece.
² Laboratory of Biology, Department of Medicine, School of Health Sciences, University of Ioannina, Ioannina, Greece.
³ Laboratory of Pharmacognosy, Division of Pharmacognosy- Pharmacology, Faculty of Health Sciences, School of Pharmacy, Aristotle University of Thessaloniki, 541 24 Thessaloniki, Greece.
⁴ Zoology Laboratory Department of Biological Application and Technology, University of Ioannina, 45110 Ioannina, Greece.

PMID: 31755397
DOI: 10.2174/1871520619666191121110848

Abstract

Background: Glioblastoma is the most common primary brain tumor in adults with a dismal prognosis. To date, several anticancer agents have been isolated from plants. Helleborus odorus subsp. Cyclophyllus is an endemic plant of the Balcan flora. Herewith, we investigated for the first time, the anti-glioma effect of deglucohellebrin (DGH) extracted from the roots of Helleborus.

Methods: We investigated the effect of DGH in U251MG, T98G and U87G glioblastoma cell lines. We selected the T98G cells because of their inherent temozolomide resistance.

Results: The IC50 value of reduced viability for DGH was 7x10-5M in U251MG cells, 5x10-5M for the T98G cells and 4x10-5M in U87G cells during 72h treatment. DGH induced G2/M cell cycle arrest, caspace-8 activation and significant mitochondrial membrane depolarization, suggesting the activation of the intrinsic, mitochondrial- dependent apoptotic pathway. DGH and temozolomide induced changes in CDs' expression in U251MG and T98G cells. In zebrafish, DGH did not induce toxicity or behavioral alterations.

Conclusion: The present study is the first to determine the anti-glioma activity of DGH. DGH may be a potent agent for glioblastoma treatment and further studies are needed.

Keywords: G2/M cell cycle arrest; Glioblastoma; deglucohellebrin; prognosis; treatment; zebrafish..

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology*
Brain Neoplasms / drug therapy*
Brain Neoplasms / pathology
Cell Cycle Checkpoints / drug effects
Cell Proliferation / drug effects
Cell Survival / drug effects
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Glioblastoma / drug therapy*
Glioblastoma / pathology
Humans
Molecular Conformation
Structure-Activity Relationship
Tumor Cells, Cultured
Zebrafish

Substances

Antineoplastic Agents