120P - Glioblastoma multiforme overcomes ultrasmall superparamagnetic iron oxide nanoparticle induced cytotoxicity through heat shock protein protective m...

Date 18 November 2017
Event ESMO Asia 2017 Congress
Session Poster lunch
Topics Central Nervous System Malignancies
Translational Research
Presenter Tsz Wai Rosita Pang
Citation Annals of Oncology (2017) 28 (suppl_10): x35-x38. 10.1093/annonc/mdx657
Authors T.W.R. Pang1, G. Fatseas1, M.E. Koina2, S. Adamson1, S. Wilkinson3, T. Chan-Ling1
  • 1Department Of Anatomy And Histology, Bosch Institute, University of Sydney, 2006 - Sydney/AU
  • 2Department Of Anatomical Pathology, , Act Pathology, The Canberra Hospital, 2605 - Canberra/AU
  • 3School Of Chemistry, Faculty Of Science, University of Sydney, 2006 - Sydney/AU



Glioblastoma Multiforme (GBM) is an aggressive brain cancer associated with high mortality. Current treatments including resection of 98% or more of the tumour result in median survival of less than 15 months. With such poor outcomes, innovative therapies are required. Ultrasmall Superparamagnetic Iron Oxide Nanoparticles (USPIONs) are emerging as potential treatments, however little is known on their effects on cells. Understanding interactions between USPIONs and GBM is critical in developing these therapies. The aim of this study is to investigate biological effects of USPION uptake on GBM cells in vitro.


CNS-1 cell cultures were exposed to 20µg/mL of USPIONs with a maghemite iron oxide cores, which mean core diameters are 10–15 nm. In order to measure the intake and the interaction of USPIONs on CNS-1, we have utilized different techniques including the transmission electron microscopy (TEM), iron quantification, mitochondrial membrane potential assay, Oxidative Stress Test, Mitochondrial Transition Pore Assay, flow cytometry, immunohistochemistry and western blotting.


Our results showed that USPIONs entered CNS-1 cells via clatherin coated pits which then became internalized in vacuoles. USPIONs induced Fenton Reaction, which potentially leads to the oxidative stress activating the Heat Shock Proteins (HSPs) protective mechanism. When this mechanism was overwhelmed, it led to a decrease in cell viability, however in due course, cells upregulated HSPs, re-activating these protective mechanisms which included the closure of mitochondrial permeability transition pore, limiting the release of pro-apoptotic cytochrome c, reducing oxidative stress and eventually recovering cell viability.


Ultrasmall superparamagnetic iron oxide nanoparticles interact with CNS-1, initiating the mitochondrial death pathway, however heat shock proteins are recruited, mitigating further apoptosis. Targeting CNS-1 protective mechanisms in conjunction with USPIONs exposure could induce a cytotoxic effect on CNS-1, providing insights for a novel therapy for this devastating disease.

Clinical trial identification

Legal entity responsible for the study

Tailoi Chan-Ling




All authors have declared no conflicts of interest.