Phytochemicals - an alternative therapy for glioblastoma?

INTRODUCTION: Glioblastoma is the most common and malignant primary brain tumour in adults. Despite current treatment options including surgery followed by radiation and chemotherapy with temozolomide (TMZ) and cisplatin,... [ view full abstract ]

INTRODUCTION: Glioblastoma is the most common and malignant primary brain tumour in adults. Despite current treatment options including surgery followed by radiation and chemotherapy with temozolomide (TMZ) and cisplatin, median survival rates remain low (<16 months).  Combined with increasing drug resistance and the inability of some compounds to cross the blood brain barrier (BBB), novel compounds are being sought for the treatment of this disease.  Phytochemicals are bioactive, non-nutrient plant chemicals which are structurally sub-divided into 5 groups.  Of these groups, phenolics are the most common and widely studied, with flavonoids being the most abundant.  With their reduced side-effect profile and ability to cross the BBB, phytochemicals offer potential to improve current glioblastoma treatment options.  METHODS: High performance liquid chromatography (HPLC) was undertaken to identify and measure individual polyphenols present in five freeze-dried fruit samples (acai berry, maqui berry, goji berry, strawberry and cranberry).   Subsequently, SVG-p12 and U87-MG cells were treated with varying concentrations of cisplatin, punicalagin or cyanidin-3-glucoside over a 3-day period. Concentration dependent effects of each treatment on cell viability were measured by the addition of PrestoBlue® reagent. Fluorescence was measured at Ex 535nm/Em 612nm.  RESULTS: Following treatment, a time and concentration-dependent reduction in cell viability was observed.  In U87-MG and SVG-p12 cells after 48 hours of treatment, IC₅₀ values for punicalagin were 46 and 49µM respectively.  Interestingly, cyanidin-3-glucoside did not reduce cell viability in SVG-p12 cells to the same extent as in U87-MG cells with IC₅₀ values of 109 and 46µM respectively. Cisplatin showed similar efficacy in both cells lines following 48 hours of treatment with IC₅₀ values of 10µM and 7mM in SVG-p12 and U87-MG cells respectively.  CONCLUSION: This data suggests that the phenolic compounds punicalagin and cyanidin-3-glucoside have cytotoxic effects on glioma cell lines and have the potential to become alternative treatments for glioblastoma.