Targeting Glioma Stem Cells by Functional Inhibition of Dynamin 2: A Novel Treatment Strategy for Glioblastoma

Rodney Luwor; Andrew P Morokoff; Stephanie Amiridis; Giovanna D'Abaco; Lucia Paradiso; Stanley S Stylli; Hong P T Nguyen; Mark Tarleton; Kelly A Young; Terence J O'Brien; Phillip J Robinson; Megan Chircop; Adam McCluskey; Nigel C Jones

doi:10.1080/07357907.2019.1582060

Targeting Glioma Stem Cells by Functional Inhibition of Dynamin 2: A Novel Treatment Strategy for Glioblastoma

Cancer Invest. 2019;37(3):144-155. doi: 10.1080/07357907.2019.1582060. Epub 2019 Mar 25.

Authors

Rodney Luwor¹, Andrew P Morokoff^{1

2}, Stephanie Amiridis^{1

3}, Giovanna D'Abaco⁴, Lucia Paradiso¹, Stanley S Stylli^{1

2}, Hong P T Nguyen¹, Mark Tarleton⁵, Kelly A Young⁵, Terence J O'Brien^{3

6

7}, Phillip J Robinson^{5

8}, Megan Chircop^{5

8}, Adam McCluskey⁵, Nigel C Jones^{3

6

7}

Affiliations

¹ a Department of Surgery , The University of Melbourne, The Royal Melbourne Hospital , Parkville , Australia.
² b Department of Neurosurgery , The Royal Melbourne Hospital , Parkville , Australia.
³ c Department of Medicine , The University of Melbourne, The Royal Melbourne Hospital , Parkville , Australia.
⁴ d Melbourne School of Engineering, School of Chemical and Biomedical Engineering , The University of Melbourne , Parkville , Australia.
⁵ e Department of Chemistry, School of Environmental and Life Sciences , The University of Newcastle , Callaghan , Australia.
⁶ f Department of Neuroscience , Central Clinical School, Monash University , Melbourne , Australia.
⁷ g Department of Neurology , The Alfred Hospital , Melbourne , Australia.
⁸ h Children's Medical Research Institute, The University of Sydney , Westmead , Australia.

PMID: 30907150
DOI: 10.1080/07357907.2019.1582060

Abstract

Glioma stem cells (GSCs) play major roles in drug resistance, tumour maintenance and recurrence of glioblastoma. We investigated inhibition of the GTPase dynamin 2 as a therapy for glioblastoma. Glioma cell lines and patient-derived GSCs were treated with dynamin inhibitors, Dynole 34-2 and CyDyn 4-36. We studied about cell viability, and GSC neurosphere formation in vitro and orthotopic tumour growth in vivo. Dynamin inhibition reduced glioblastoma cell line viability and suppressed neurosphere formation and migration of GSCs. Tumour growth was reduced by CyDyn 4-36 treatment. Dynamin 2 inhibition therefore represents a novel approach for stem cell-directed Glioblastoma therapy.

Keywords: Cancer biology; Cancer stem cells; Dynamin; Glioblastoma; Invasion.

MeSH terms

Brain Neoplasms / drug therapy*
Brain Neoplasms / metabolism
Brain Neoplasms / pathology
Cell Line, Tumor
Cell Movement / drug effects
Cell Proliferation / drug effects
Cyanoacrylates / therapeutic use*
Dynamin II / antagonists & inhibitors*
Dynamin II / metabolism
Glioma / drug therapy*
Glioma / metabolism
Glioma / pathology
Humans
Indoles / therapeutic use*
Molecular Targeted Therapy / methods
Neoplastic Stem Cells / drug effects*
Neoplastic Stem Cells / metabolism
Tumor Burden / drug effects
Xenograft Model Antitumor Assays

Substances

Cyanoacrylates
Indoles
dynole 34-2
Dynamin II