Author: Al Mohammad Yunus Soni
Soni, Al Mohammad Yunus, 2023 Inhibition of Glioblastoma Cells Invasiveness using Novel Natural Compounds, Flinders University, College of Medicine and Public Health
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Glioblastoma multiforme is highly aggressive and the most malignant form of brain cancer. Glioblastoma has high invasiveness rates, with a very short average survival duration of roughly 10 months, despite the use of optimal treatment. The present therapeutic approach includes a combination of surgical excision, chemotherapy with temozolomide (TMZ) and radiation. Tumours often recur post-treatment and cells may develop resistance to TMZ However, no novel chemotherapy drugs have been introduced since 2005. The Griffith Institute of Drug Discovery (GRIDD) has identified several compounds derived from NatureBank that have therapeutic potential for various illnesses and pathologies (Liberio et al, 2015). It is hypothesised that these compounds may possess anti-cancer properties specifically in the context of glioblastoma.
The aim of this research was to assess the potential anti-cancer activity of four NatureBank compounds, namely SN356, SN360, SN361, and SN367, in both pediatric and adult glioblastoma cell lines. These four compounds were chosen as these compounds are derivatives of 1 parent compound. In the first objective, an assessment was conducted to determine the potential cytotoxicity of each of these drugs in the three cell lines.
None of the four compounds tested on each cell line exhibited any cytotoxic effects at all concentrations examined, which were 0.03μM, 0.1μM, 0.3μM, and 1μM. Cells treated with these four compounds were subjected to a transwell invasion assay at the same concentrations used in the cytotoxicity assay. This assay aimed to evaluate the potential of these compounds in inhibiting the invasiveness of glioblastoma cells. The data from transwell assays was analyzed to determine the half-maximal inhibitory concentration (IC50) of the different compounds in the three cell lines. The observed values for the U251 cell line ranged from 0.13μM to 1.20μM, for the DBTR cell line, the values ranged from 0.13μM to 0.24μM and for the KNS42 cell line values ranged from 0.11μM to 0.07μM. These values (sub-micromolar concentrations) indicate that the compounds tested exhibit potent efficacy in restricting the invasiveness of glioblastoma.
However, further research is required to ascertain the specific mechanisms by which these compounds work.
Keywords: Glioblastoma, natural compounds, cell motility, Invasion
Subject: Biotechnology thesis
Thesis type: Masters
Completed: 2023
School: College of Medicine and Public Health
Supervisor: Dr. Sunita Ramesh , Dr. Liu-Fei Tan