Author: Aumio Ishaat
Ishaat, Aumio, 2025 Mechanistic insights into the action of eight novel compounds that limit Glioblastoma invasion, Flinders University, College of Medicine and Public Health
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Glioblastoma is one of the deadliest forms of brain cancer, affecting around 3 people in every 100,000 and has a very low 5-year survival rate at below 5%. Cancer is also highly recurring, with a highly heterogenous cell population that can quickly adapt to selective pressures placed by the current forms of therapy, which are surgery, followed by radiation and temozolomide chemotherapy. There is evidence that these therapies drive resistance and make treatment even more difficult, therefore newer and safer therapies are necessary. There is very little work done on stopping glioblastoma’s ability to invade into brain tissue, away from the central mass. One of the key ways it does so is by excreting matrix metalloproteinases (MMP) 2 and 9 into the surrounding extracellular matrix and carving pathways for the cancer cells to move through. The aim of this study was to screen 8 novel, natural compounds from the Griffith Institute of Drug Discovery’s NatureBank on two adult glioblastoma cell lines – U251-MG and DBTR-05MG on their ability to inhibit cell invasion. The compounds needed to be non-cytotoxic, so that do not place a selective pressure on the cancer cells to become resistant, and to ease the burden of side effects on patients. To do this, AlamarBlue cell viability assays were carried out on cell cultures in 96-well cell culture plates. Secondly, media samples where cells were grown had been run through pre-cast zymographic gels to observe whether the compounds inhibit MMP-2 and MMP-9, key enzymes involved in allowing cells to invade brain tissue. Future work needs to focus on using RT-qPCR to determine whether these compounds exert their effect by affecting gene expression.
Keywords: Glioblastoma, invasion, anti-invasive, MMP-2, MMP-9, natural compounds
Subject: Medical Biotechnology thesis
Thesis type: Masters
Completed: 2025
School: College of Medicine and Public Health
Supervisor: Dr. Sunita Ramesh