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Anticancer Agents Med Chem. 2019 Nov 20. doi: 10.2174/1871520619666191121110848. [Epub ahead of print]

Deglucohellebrin. A Potent Agent for Glioblastoma Treatment.

Author information

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.

Abstract

BACKGROUND:

Glioblastoma is the most common primary brain tumor in adults with 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 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 72-h treatment. DGH induced G2/M cell cycle arrest, caspace-8 activation and significant mitochondrial membrane depolarization suggesting 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:

Deglucohellebrin; G2/M cell cycle arrest; Glioblastoma; Prognosis; Treatment; Zebrafish

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