Pankiller effect of prolonged exposure to menadione on glioma cells: potentiation by vitamin CReport as inadecuate

Pankiller effect of prolonged exposure to menadione on glioma cells: potentiation by vitamin C - Download this document for free, or read online. Document in PDF available to download.

Investigational New Drugs

, Volume 29, Issue 6, pp 1314–1320

First Online: 13 July 2010Received: 24 May 2010Accepted: 24 June 2010 Summary

Menadione Vitamin K3 has anti-tumoral effects against a wide range of cancer cells. Its potential toxicity to normal cells and narrow therapeutic range limit its use as single agent but in combination with radiation or other anti-neoplastic agents can be of therapeutic use. In this paper, we first evaluated the early within 3 h effect of menadione on ongoing DNA replication. In normal rat cerebral cortex mini-units menadione showed an age dependent anti-proliferative effect. In tissue mini-units prepared from newborn rats, menadione inhibited ongoing DNA replication with an IC 50 of approximately 10 μM but 50 μM had no effect on mini-units from prepared adult rat tissue. The effect of short 72 h and prolonged exposure 1–2 weeks to menadione alone in the DBTRG.05MG human glioma cells line and in combination with vitamin C was studied. After short period of exposure data show that menadione alone or in combination with vitamin C provided similar concentration-response curves and IC50 values. Prolonged exposure to these drugs was evaluated by their ability to kill 100% of glioma cells and prevent regrowth when cells are re-incubated in drug-free media. In this long-term assay, menadione:vitamin C at a ratio 1:100 showed higher anti-proliferative activity when compared to each drug alone and allowed to reduce each drug concentration between 2.5 to 5-fold. Similar anti-proliferative effect was demonstrated in 8 patient derived glioblastoma cell cultures. Our data should be able to encourage further advanced studies on animal models to evaluate the potential use of this combination therapy for glioma treatment.

KeywordsGliomas Menadione Vitamin C Proliferation DNA replication Marina F. Vita and Nivedita Nagachar contributed equally to this work.

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Author: Marina F. Vita - Nivedita Nagachar - Dimitrios Avramidis - Zahid M. Delwar - Mabel H. Cruz - Åke Siden - Kajsa M. Paul


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