Characterisation of the in vitro effects of Asiatic acid in Glioblastoma

Thakor, Flourina Kumar (2016) Characterisation of the in vitro effects of Asiatic acid in Glioblastoma. Doctoral thesis, University of Central Lancashire.

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Glioma arises from glial cells in the brain and is the most common intracranial neoplasm of the central nervous system. It is known that tumour masses are hypoxic and a drop in the partial pressure of oxygen activates hypoxia inducible factor that plays an important role in tumour growth by controlling the transcription of genes responsible for cell proliferation, angiogenesis and energy metabolism. Asiatic acid, a pentacyclic triterpenoid extracted from Centella asiatica, has shown cytotoxicity against many cancer cell lines.

To determine its anti-cancer effects under hypoxia, we investigated the effects of asiatic acid on U87-MG cell line, a grade IV glioblastoma cell line under normoxia and 1% & 5% hypoxia. Asiatic acid efficacy on glioblastoma cells was assessed using fluorescent dyes along with flow cytometric and microscopic analysis. A major problem associated with the administration of asiatic acid is low aqueous solubility thus hindering dissolution and causing decreased bioavailability. Thus we formulated asiatic acid-loaded poly-ε-caprolactone nanoparticles for sustained and localised delivery in glioblastoma cells in vitro.
Asiatic acid nanoparticles were prepared using solvent displacement method and showed an average diameter of 150nm, average negative surface charge of
-20mV and were stable for a minimum of 60 days at 4°C. Results showed no drug release or nanoparticle degradation in the absence of lipase in aqueous media.
Nanoparticles were stable in PBS and presence of lipase enhanced drug release. Asiatic acid reduced cell viability in U87-MG cell line in a time and concentration-dependent manner. Flow cytometric analysis revealed a large number of cells undergoing cell death via apoptosis under normoxia. A significant delay in wound healing was observed with asiatic acid treatment under normoxia and a only partial closure of the wound was observed following 18 hours of incubation. Under hypoxia, a significantly large number of cells underwent apoptosis in comparison to the chemotherapy drug cisplatin. We did not observe any significant effects on cell proliferation or cell cycle.

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