PMID: 9524088Apr 2, 1998Paper

Vinca-alkaloid neurotoxicity measured using an in vitro model

Journal of Neuro-oncology
A A GeldofJ J Heimans

Abstract

Neurotoxicity forms a major limitation in many clinical applications of vincristine and other powerful vinca alkaloid anticancer drugs. Using the nerve growth factor (NGF) dependent neurite outgrowth from the PC12 pheochromocytoma cell line as an in vitro assay for neurotoxicity, the effect of different concentrations of vincristine (0.55; 1.1 and 11 nM) was compared with that of vindesine and vinblastine. Vincristine in comparatively low concentration (0.55 nM) could significantly decrease the percentage of neurite forming cells from 74% to 32% within a three day incubation period. Especially the longer neurites (> 2 x cell body) proved to be extremely sensitive for vincristine effects. Vinblastine and vindesine were also able to decrease, dose dependently and significantly, the percentage of neurite forming cells. However, the effects observed were less severe than that of vincristine. The sequentially increasing level of neurotoxicity due to vinblastine, vindesine and vincristine, as observed in the neurite outgrowth inhibition correlates well with previous findings from animal models and with data from the clinical practice. Withdrawal of vincristine resulted in a rapid restoration of neurite formation, suggesting the poten...Continue Reading

Citations

Sep 13, 2003·Journal of Neurochemistry·Guang Jian WangStanley A Thayer
Mar 15, 2015·The Oncologist·Abolfazl AvanGodefridus J Peters
Jun 10, 2008·Toxicological Sciences : an Official Journal of the Society of Toxicology·Nicholas M RadioWilliam R Mundy

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