Cruz T F, Morgan A, Min W
Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Canada.
Mol Cell Biochem. 1995;153(1-2):161-6. doi: 10.1007/BF01075933.
In the present study we have demonstrated that orthovanadate at concentrations of 5-10 uM is cytotoxic to proliferating cells including primary cultures and tumour cell lines. However, concentrations of up to 50 uM 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 mechanisms 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 5 uM has antineoplastic properties and may be useful as a chemotherapeutic agent.
在本研究中,我们已证明浓度为5 - 10微摩尔的原钒酸盐对包括原代培养细胞和肿瘤细胞系在内的增殖细胞具有细胞毒性。然而,高达50微摩尔的浓度并未影响非增殖细胞的活力。细胞毒性似乎取决于钒的浓度,而非钒的氧化态或钒化合物。此外,具有不同增殖速率的肿瘤细胞系对原钒酸盐的细胞毒性同样敏感。尽管导致细胞毒性的机制尚不清楚,但添加过氧化氢可增强原钒酸盐的细胞毒性,这表明羟基或钒自由基可能参与其中。在体内,向含有MDAY - D2肿瘤的小鼠皮下注射原钒酸盐导致肿瘤生长受到85 - 100%的抑制。这些数据表明,浓度大于5微摩尔的原钒酸盐具有抗肿瘤特性,可能作为一种化疗药物有用。