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  • Title: The antineoplastic drug lonidamine interferes with the acidification mechanism of cell organelles.
    Author: Dell'Antone P, Piergallini L.
    Journal: Biochim Biophys Acta; 1997 Aug 21; 1358(1):46-52. PubMed ID: 9296520.
    Abstract:
    The effect of the anticancer drug lonidamine (LND) on the pH of intracellular organelles was studied in isolated rat thymocytes by fluorimetric analysis of the (bafilomycin-nigericin sensitive) uptake of the acridine orange dye (AO) into acidic compartments. LND brought about a marked reduction (> 60%) in the above pH gradients with a half maximal decrease at a concentration of 0.25 mM. LND also caused a decrease, although to a lesser extent, in the ATP levels. In isolated rat liver lysosomes, 0.6 mM LND was found to inhibit ATP-driven organelle acidification by about 80%; minor inhibition of ATPase activity was observed in the same conditions. In addition, LND was able to promote proton efflux from isolated lysosomes. On the basis of our results it is suggested that the effect of LND on intracellular proton gradients may be due partially to the decrease in ATP levels, and mostly to a drug-induced increase in the ion (proton) permeability of the membranes.
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