Noscapine: a study of its effects on the glioma vasculature

UnrestrictedNoscapine has been widely used as an oral antitussive agent. More recently, studies have shown that noscapine significantly affects microtubule dynamics and has potent antitumor and antiangiogenic activity. The aim of our study was to investigate noscapine's effects in glioblastoma multiforme (GBM) focusing on its effects on the glioma vasculature. We studied the effects of noscapine on cytotoxicity, migration and cytokine secretion of normal (BEC) and tumor-associated brain endothelial cells (TuBEC). We found that noscapine significantly decreased migration of both BEC and TuBEC. In accordance with this, we found that noscapine also decreased microvessel density in vivo.; Since noscapine has been shown to be effective against a wide variety of cancers, we hypothesized that it may also be effective against glioma. Our study has indicated that noscapine at 550 mg/kg/day significantly delayed tumor progression in a subcutaneous murine model of human glioma without any observable side effects. Moreover, noscapine alone significantly prolonged survival in mice implanted intracranially with human glioma cells but it was not synergistic with temozolomide. However, in temozolomide-resistant tumors, noscapine and TMZ are very synergistic.; Our studies showed that noscapine has potential as an antitumor and antiangiogenic agent for GBM. To date, most studies on noscapine have been done on mouse or rat gliomas. The novel aspect of our study is that we investigated noscapine's effects on human glioma and the associated vasculature. BEC and TuBEC used in our study were isolated from patients with GBM and thus make for an excellent model. GBM, being a highly vascular tumor is dependent on angiogenesis for tumor growth and progression. Noscapine attacks both the tumor cells and the vasculature feeding the tumor simultaneously and this makes it an attractive drug for GBM treatment. Moreover, it chemosensitizes TMZ-resistant tumors to TMZ and may thus be effective in treating tumors that are no longer responsive to temozolomide