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