GALLIUM-PYRIDOXAL ISONICOTINOYL HYDRAZONE (GA-PIH), A NOVEL CYTOTOXICGALLIUM COMPLEX - A COMPARATIVE-STUDY WITH GALLIUM NITRATE

The anti-proliferative activity of gallium-pyridoxal isonicotinoyl hyd razone (Ga-PIH) a novel gallium complex was compared with that of gall ium nitrate, a known anti-tumor agent At 50 mu M, Ga-PIH inhibited CCR F-CEM cell growth by 45% compared to <10% inhibition with gallium nitr ate or PIH. The IC(50)s for Ga-PIH, gallium nitrate and PIH were 60, 8 4 and 68 mu M respectively. The addition of exogenous iron as transfer rin-iron to the culture medium reversed the cytotoxicity of gallium ni trate and PIH in a dose- dependent manner but had only minor effects o n the cytotoxicity of Ga-PIH. The effect of these compounds on cellula r iron uptake was measured since prior studies have shown that gallium perturbs iron transport into cells. Fifty micromolar Ga-PIH, gallium nitrate or PIH inhibited the cellular uptake of Fe-59-transferrin over 24 h by 65%, 32 % and 78% respectively. Although all three compounds inhibited iron uptake, only Ga-PIH produced a significant upregulation of cellular transferrin receptors. Since the cytotoxicity of Ga-PIH a ppears to be less influenced by extracellular iron and cellular transf errin receptor expression, it may have potential as an antineoplastic agent and should be further evaluated in animal tumor models.