Supplementary Material for: Inhibition of the Mevalonate Pathway Targets Neuroblastoma Stem Cells

Introduction:
High-risk neuroblastoma is a difficult to treat cancer with high rates of recurrence and treatment resistance, likely driven by a population of cancer stem cells. Multiple previous studies have suggested that the use of mevalonate pathway inhibitors, such as statins and bisphosphonates, may have anticancer activity against high-risk tumors.

Methods:
We aimed to observe the use of mevalonate pathway inhibitors against the cancer stem cell population of high-risk neuroblastoma cell lines SH-SY5Y, SK-N-AS, and SK-N-BE(2)-C using spheroid-based assays.

Results:
We observed significant reductions in spheroid formation capability, stem cell frequency, and stemness properties of these neuroblastoma cancer stem cells with fluvastatin and zoledronate treatment.

Conclusion:
Treatment with mevalonate pathway inhibitors leads to reduced neuroblastoma cancer stem cell function through reductions in protein geranylgeranylation.

Key words: neuroblastoma, mevalonate, statin, bisphosphonate, spheroids, spheres, cancer stem cells