title: Pharmacological effects of asiatic acid in glioblastoma cells under hypoxia.
abstract: Glioblastoma multiforme is the most common and malignant primary brain tumor in adults. Despite current treatment options including surgery followed by radiation and chemotherapy with temozolomide and cisplatin, the median survival rate remains low (<16 months). Combined with increasing drug resistance and the inability of some compounds to cross the blood-brain barrier, novel compounds are being sought for the treatment of this disease. Here, we aimed to examine the pharmacological effect of Asiatic acid (AA) in glioblastoma under hypoxia. To investigate the effects of AA on cell viability, proliferation, apoptosis, and wound healing, SVG p12 fetal glia and U87-MG grade IV glioblastoma cells were cultured under normoxic (21% O2) and hypoxic (1% O2) conditions. In normoxia, AA reduced cell viability in U87-MG cells in a time and concentration-dependent manner. A significant decrease in viability, compared to cisplatin, was observed following 2 h of AA treatment with no significant changes in cell proliferation or cell cycle progression observed. Under hypoxia, a significantly greater number of cells underwent apoptosis in comparison to cisplatin. While cisplatin showed a reduction in wound healing in normoxia, a significantly greater reduction was observed following AA treatment. An overall reduction in wound healing was observed under hypoxia. The results of this study show that AA has cytotoxic effects on glioma cell lines and has the potential to become an alternative treatment for glioblastoma.
authors.affiliation: School of Pharmacy and Biomedical Sciences, University of Central Lancashire, Preston, Lancashire, PR1 2HE, UK.
authors.forename: Flourina Kumar
authors.initials: FK
authors.lastname: Thakor
authors.affiliation: School of Pharmacy and Biomedical Sciences, University of Central Lancashire, Preston, Lancashire, PR1 2HE, UK.
authors.forename: Ka-Wai
authors.initials: KW
authors.lastname: Wan
authors.affiliation: School of Pharmacy and Biomedical Sciences, University of Central Lancashire, Preston, Lancashire, PR1 2HE, UK.
authors.forename: Philip John
authors.initials: PJ
authors.lastname: Welsby
authors.affiliation: School of Pharmacy and Biomedical Sciences, University of Central Lancashire, Preston, Lancashire, PR1 2HE, UK. GWelsby@uclan.ac.uk.
authors.forename: Gail
authors.identifier: http://orcid.org/0000-0001-9901-7627
authors.initials: G
authors.lastname: Welsby
mesh_terms: D002453:Cell Cycle / Q000187:drug effects*; D015687:Cell Hypoxia / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005909:Glioblastoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D053978:Pentacyclic Triterpenes / Q000494:pharmacology*
chemical_list: D053978:Pentacyclic Triterpenes; C017032:asiatic acid
keywords: Asiatic acid; Glioblastoma; Hypoxia; U87-MG