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Pankiller effect of prolonged exposure to menadione on glioma cells: potentiation by vitamin C

Vita, Marina F.; Nagachar, Nivedita LU ; Avramidis, Dimitrios; Delwar, Zahid M.; Cruz, Mabel H.; Siden, Ake; Paulsson, Kajsa M LU and Yakisich, Juan Sebastian (2011) In Investigational New Drugs 29(6). p.1314-1320
Abstract
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 mu M but 50 mu M had no effect on mini-units from prepared adult rat tissue. The effect of short (72 h) and prolonged exposure (1-2... (More)
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 mu M but 50 mu M 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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Gliomas, Menadione, Vitamin C, Proliferation, DNA replication
in
Investigational New Drugs
volume
29
issue
6
pages
1314 - 1320
publisher
Springer
external identifiers
  • wos:000294824200020
  • scopus:84856024885
ISSN
0167-6997
DOI
10.1007/s10637-010-9489-0
language
English
LU publication?
yes
id
57c64b79-aa83-4c25-afab-eb4f93794d8e (old id 2186905)
date added to LUP
2011-11-01 07:52:41
date last changed
2017-08-06 04:04:17
@article{57c64b79-aa83-4c25-afab-eb4f93794d8e,
  abstract     = {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 mu M but 50 mu M 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.},
  author       = {Vita, Marina F. and Nagachar, Nivedita and Avramidis, Dimitrios and Delwar, Zahid M. and Cruz, Mabel H. and Siden, Ake and Paulsson, Kajsa M and Yakisich, Juan Sebastian},
  issn         = {0167-6997},
  keyword      = {Gliomas,Menadione,Vitamin C,Proliferation,DNA replication},
  language     = {eng},
  number       = {6},
  pages        = {1314--1320},
  publisher    = {Springer},
  series       = {Investigational New Drugs},
  title        = {Pankiller effect of prolonged exposure to menadione on glioma cells: potentiation by vitamin C},
  url          = {http://dx.doi.org/10.1007/s10637-010-9489-0},
  volume       = {29},
  year         = {2011},
}