Author: Aparna Bindu
Bindu, Aparna, 2022 Screening natural compound extracts for potential anti-cancer activity on glioblastoma cell line U251-MG, Flinders University, College of Medicine and Public Health
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Glioblastoma multiforme is the most malignant and aggressive form of brain cancer in adults. Its highly invasive nature results in poor prognoses and even with the best treatment, median survival of patients is 15 months. Current treatments involving surgical resection, radiotherapy and temozolomide (TMZ) have remained unchanged since 2005. Bioactive compounds extracted from plants, fungi and marine invertebrates have been a source of natural compounds used to treat many diseases and pathologies.
This study investigated the potential of root extracts of a traditional Chinese medicinal herb Sophora flavescens (Kushen) and a library of natural compound extract fractions from NatureBank in inhibiting glioblastoma cell invasion using U251MG cells. In the first aim, transwell invasion assay used to screen NatureBank compound extract library identified twenty compounds that inhibited invasion of U251MG cells (invasion percentages from 6.5% to 53%). In the second aim, all the twenty compounds were tested for cytotoxicity at different concentrations (0.03 to 1 µM). No cytotoxicity was detected for any of the compounds. Four compounds (3-Methylbut-3-enyl-O-a-L-rhamno-pyranosyl-(1-6)-O-b-D-glucopyranoside; Xanthurenic acid and two novel compounds) were selected for further study. Half maximal inhibitory concentrations (IC50) of these compounds ranged from 0.24 to 0.43 µM. In the third aim, root extracts of Kushen were tested for their effect on limiting invasion of U251MG cells. A concentration of 50 µg/ml was effective in inhibiting invasion of cells by 57%.
The outcomes of this study are the identification of 20 natural compounds that were effective in limiting glioblastoma invasion. Further work needs to be conducted to identify the mode of action of these compounds.
Keywords: Glioblastoma, GBM, transwell invasion, anti-cancer, Kushen, traditional Chinese medicine, Compound Kushen Injection, CKI, NatureBank, natural compounds, inhibition of invasion, U251MG
Subject: Biotechnology thesis
Thesis type: Masters
Completed: 2022
School: College of Medicine and Public Health
Supervisor: Dr. Sunita Ramesh