Medulloblastoma (MB) is characterized as a grade IV embryonal brain tumor that primarily affects children. Standard treatments for medulloblastoma include radiation and chemotherapeutic agents. The current chemotherapeutic options available for MB have several limitations and severe long term toxic effects. The chemotherapeutic limitations drive researchers to search for new or modified therapies, even with the use of natural products such as berberine chloride (BBC). Berberine chloride (BBC), which is naturally derived from the Berberis plant, have been reported in the literature to inhibit breast cancer cell growth, however its anti-cancer activity has not been studied in either MB or other brain tumors. In our current study, our objective was to evaluate the individual and combination treatment of a chemotherapeutic agent, vincristine (VCR), [Cu(TA)₂(bpy)] (where TA = tolfenamic acid and bpy = 2,2’-bipyridine), and BBC against MB cells. It is hypothesized that the combination therapy of [Cu(TA)₂(bpy)]and BBC will be more effective in inhibiting medulloblastoma cell growth and overall prove to be a more effective cancer treatment. The MB cell line, DAOY, was obtained from ATCC. The anti-proliferative activity of VCR, [Cu(TA)₂(bpy)], BBC, and combination treatments against DAOY cells were evaluated with the use of CellTiterGlo kit. To determine appropriate combination dosages, dose curves were established based on cell viability data. IC₅₀ values were established using GraphPad software. The levels of caspase 3/7 and ROS were determined using luminescent kits. The results revealed that VCR, [Cu(TA)₂(bpy)], and BBC inhibited MB cell growth. A more significant effect occurred when treatments were administered as combination therapy. Our results showed that [Cu(TA)₂(bpy)] and BBC were successful at inhibiting medulloblastoma cell growth, while continuing to evaluate the effects of the treatments as a combination therapy. It can be concluded TA and [Cu(TA)₂(bpy)], when used in combination with vincristine, was found to increase the anti-proliferative efficacy against MB cells. Due to its effect on specific targets associated with cancer (e.g., Specificity protein 1 and Survivin) combining [Cu(TA)₂(bpy)] with BBC may be more effective in treating medulloblastoma. If successful, this study may be helpful to develop effective therapeutic strategies while decreasing the prolonged adverse effects in MB patients due to multimodality therapy.

Christoffer Lambring

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