Aim: The treatment of pediatric low-grade gliomas with current treatment modalities still remains ineffective among a subset of patients; hence, justifying the need to further investigate more effective therapies. Dipotassium bisperoxo (picolinato) oxovanadate V (Bpv[pic]), is a derivative of the trace metal vanadium and a potent inhibitor of protein tyrosine phosphatases, which are important mediators of oncogenic and tumor suppressive activities in cancers. In this study, we undertook a preclinical evaluation of the antineoplastic functions of Bpv(pic) in the treatment of pediatric low-grade gliomas.
Materials & methods: We utilized pediatric low-grade glioma cell lines (Res186, Res259 and R286) in a wide variety of cancer assays to determine whether Bpv(pic) can abrogate the neoplastic properties of these cells.
Results: Our preclinical evaluation of the antineoplastic properties of Bpv(pic) in pediatric low-grade gliomas reveals a significant dose-dependent decrease in cell viability as a consequence of decreased proliferation and sustained induction of growth arrest and apoptosis. Bpv(pic) significantly decreases cell migration/invasion and anchorage-independent growth in soft agarose. Within cells, Bpv(pic) functions by attenuating CDC25A activity, and by decreasing the expression of multiple protein tyrosine phosphatases, DNA repair genes, microtubule-associated genes, such as PLK1, AURKA and HDAC6, and conversely augmenting the expression of proapoptotic mediators such as BAK, AIFM and CTSL1.
Conclusion: Collectively, our data strongly suggest novel evidence of Bpv(pic) being a potent antineoplastic drug and a suitable alternative for the treatment of pediatric low-grade gliomas.