X-Message-Number: 10070
Date: Thu, 16 Jul 1998 21:29:06 -0700 (PDT)
From: Doug Skrecky <>
Subject: antineoplastic effects of orthovanadate

"In Vitro and In Vivo Antineoplastic Effects of Orthovanadate"
Molecular and Cellular Biochemistry 153: 161-166 1995


  In the present study we have demonstrated that orthovanadate at
concentrations of 0.005-0.01 mM is cytotoxic to proliferating cells
including primary cultures and tumour cell lines. However, concentrations
of up to 0.05 mM did not affect the viability of non-proliferating cells.
The cytotoxicity appears to be dependent on the vanadium concentration
rather than on the oxidation state of vanadium or the vanadium compound.
Furthermore, tumour cell lines with different proliferative rates were
equally sensitive to orthovanadate cytotoxicity. Although the mechanism
responsible for the cytotoxicity are not known, addition of H2O2
potentiated orthovanadate cytotoxicity suggesting that hydroxyl or
vanadium radicals may be involved. In vivo subcutaneous injections of
orthovanadate into mice containing MDAY-D2 tumours resulted in the
inhibition of tumour growth by 85-100%. These data indicated that
orthovanadate at concentrations greater than 0.005 mM has antineoplastic
properties and may be useful as a chemotherapeutic agent.

Further quotes from text:

"Orthovanadate cytotoxicity on tumour cell lines and drug resistant cell

  Since orthovanadate appeared to be selectively cytotoxic to proliferating
cells, we investigated the effect of orthovanadate on several tumour cell
lines. The cytotoxic effects of orthovanadate on an adherent human
astrocytoma cell line (HTB14), a mouse haematopoietic cell line (MDAY-D2)
grown in suspension and an adherent mouse endothelial cell line (EOMA) are
demonstrated in Fig. 2. Orthovanadate was cytotoxic to all of the cell
lines examined. Between 0.005-0.01 mM of orthovanadate was required for
cell toxicity, and concentrations of 0.025 mM or greater reduced cell
density by over 98% in 48 h.
  To determine whether orthovanadate is toxic to drug resistant cell lines,
we compared the effect of orthovanadate on three cell lines, KB8, KB8-5,
and KB85-11, which have increasing drug resistance respectively, relative
to the parent cell line, KB3-1. These drug resistant cell lines are not
killed by several classes of chemotherapeutic agents such as colchicine,
vinblastine and doxorubicin. As demonstrated in Fig. 4, orthovanadate was
equally cytotoxic to all of the drug resistant cell lines.

Efficacy of different forms of vanadium

  Figuare 3 compares the cytotoxic effect of orthovanadate, vanadyl sulfate
and peroxovanadate on MDAY D2 cell sultures. The cytotoxic effects of all
three vanadium compounds showed a similar concentration

Orthovanadate inhibition of tumour growth in vivo

  To determine whether orthovanadate may be useful as an antineoplastic
agent, the effect of orthovanadate treatment on a subcutaneous MDAY-D2
tumour mouse model was examined. The weight of tumours from individual mice
is demostrated in Fig. 6. Mice with small tumours (Day 5) treated daily
with 0.5 mg of orthovanadate on the opposite tumour-free posterior side for
9 days showed a significant decrease in tumour growth compared to mice
treated with vehicle alone. In control animals, the tumour weights varied
from 0.86-1.74 g, whereas in orthovanadate treated mice, four mice did not
have detectible tumours and 11 mice had tumours varying from 0.08-0.47 g.
Orthovanadate treatment either completely inhibited tumour formation or
reduced tumour growth by over 85% when compared to controls. In comparison,
the average body weight of the control group was 22.5 +- 1.7 g and the
orthovanadate treated group was 19.4 +- 2.1 g.

  ..............Thus, the higher levels of intracellular reactive oxygen
species in proliferating tumour cells may provide a mechanism to explain
the increased sensitivity of tumour cells to orthovanadate cytotoxicity.
  The present study demonstrates that orthovanadate reduced tumour growth
in mice. Subcutaneous injections of orthovanadate daily for nine days
reduced MDAY-D2 tumour growth in mice by 85-100%. Although the animals
showed some stress immediately following each injection, their body weight
over the treatment period was approximately 85-90% that of the untreated
animals. These data indicate that orthovanadate may be a useful
antineoplastic agent for the treatment of tumours, particularly drug
resistant tumours. In addition, the gastritis induced by oral
administration of orthovanadate or vanadyl sulphate may be explained by the
cytotoxic effects of these vanadium compounds on the rapidly proliferating
surface epithelial cells in the gastrointestinal tract. Whether these
general toxic effects can be abolished by conjugating vanadium with organic
molecules or by supplementing its administration with antioxidents remains
to be determined."

Addition note by poster:

  I am so impressed by vanadium's potential in chemotherapy, that until
angiostatin/endostatin therapy becomes commercially available, I believe
injections of vanadium compounds should be the last line of defence
against drug resistant tumours. I'd suggest it as a first line of defence
as well, but commercial interests being what they are, unfortunately only
patented drugs come under active consideration by doctors.

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