Deglucohellebrin: A Potent Agent for Glioblastoma Treatment

Author:

Vartholomatos Evrysthenis1,Alexiou George A.1ORCID,Markopoulos Georgios S.2,Lazari Diamanto3,Tsiftsoglou Olga3,Chousidis Ieremias4,Leonardos Ioannis4,Kyritsis Athanasios P.1

Affiliation:

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 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.

Funder

European Social Fund-ESF

Publisher

Bentham Science Publishers Ltd.

Subject

Cancer Research,Pharmacology,Molecular Medicine

Reference26 articles.

1. Liu Y.; Shete S.; Etzel C.J.; Scheurer M.; Alexiou G.; Armstrong G.; Tsavachidis S.; Liang F-W.; Gilbert M.; Aldape K.; Armstrong T.; Houlston R.; Hosking F.; Robertson L.; Xiao Y.; Wiencke J.; Wrensch M.; Andersson U.; Melin B.S.; Bondy M.; Polymorphisms of LIG4, BTBD2, HMGA2, and RTEL1 genes involved in the double-strand break repair pathway predict glioblastoma survival. J Clin Oncol 2010,28(14),2467-2474

2. Verhaak R.G.; Hoadley K.A.; Purdom E.; Wang V.; Qi Y.; Wilkerson M.D.; Miller C.R.; Ding L.; Golub T.; Mesirov J.P.; Alexe G.; Lawrence M.; O’Kelly M.; Tamayo P.; Weir B.A.; Gabriel S.; Winckler W.; Gupta S.; Jakkula L.; Feiler H.S.; Hodgson J.G.; James C.D.; Sarkaria J.N.; Brennan C.; Kahn A.; Spellman P.T.; Wilson R.K.; Speed T.P.; Gray J.W.; Meyerson M.; Getz G.; Perou C.M.; Hayes D.N.; Cancer Genome Atlas Research Network. Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell 2010,17(1),98-110

3. Kyritsis A.P.; Levin V.A.; An algorithm for chemotherapy treatment of recurrent glioma patients after temozolomide failure in the general oncology setting. Cancer Chemother Pharmacol 2011,67(5),971-983

4. Levin V.A.; Personalized medicine in neuro-oncology. CNS Oncol 2016,5(2),55-58

5. Ouyang L.; Luo Y.; Tian M.; Zhang S.Y.; Lu R.; Wang J.H.; Kasimu R.; Li X.; Plant natural products: from traditional compounds to new emerging drugs in cancer therapy. Cell Prolif 2014,47(6),506-515

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