Interference of Arsenic Trioxide on Magnesium Dependent Polymerization of Microtubule Proteins

Prevention of microtubule polymerization is considered as one of the promising approaches towards inhibition of cell proliferation, especially in treatment of malignancies. Arsenic trioxide, As2O3, is being successfully used in the treatment of human lymphoma, while the mechanism of its therapeutic function is still under investigation. Experiments were designed to determine if indeed As2O3 interferes with polymerization of nanotube microtubule. Microtubules were extracted from sheep brain and their interaction with arsenic trioxide was examined by spectrometery. Electrical conductometry of 2 mM MgSO4 solution containing various concentrations of As2O3 was studied in order to determine their possible interaction. Transmission electron microscopy was used to show microtubule structure in the presence of arsenic trioxide. Fluorometric characteristics of tubulin dimer were examined in presence of varying concentrations of arsenic trioxide. It is concluded that arsenic trioxide interacts with Mg2+ ion around GTPase site of β-tubulin, resulting enhancement of depolymerization of the microtubule polymer