Cell membrane changes induced by Lonidamine in human erythrocytes and T lymphocytes, and ehrlich ascites tumor cells

Autor: Bruno Silvestrini, C. De Martino, A. Nista, Walter Malorni, Giuseppe Formisano, L. Accinni, F. Rosati, Giuseppe Arancia
Rok vydání: 1987
Předmět:
Zdroj: Experimental and Molecular Pathology. 46:15-30
ISSN: 0014-4800
DOI: 10.1016/0014-4800(87)90027-x
Popis: Lonidamine, a derivative of indazol carboxylic acid, has been found to exert a powerful inhibitory effect on oxygen consumption and aerobic glycolysis of neoplastic cells through mechanisms yet to be defined. Recent freeze-fracture studies have shown that Lonidamine alters the distribution of intramembranous particles in the plasma membrane, suggesting that the cell membranes, rather than the energy metabolism, are the drug's primary target. The present study was carried out to further evaluate the effects of Lonidamine on cell membranes, using normal human erythrocytes and T lymphocytes and Ehrlich ascites tumor cells as cell models. These studies indicate that plasma and mitochondrial membranes are the primary site of the drug's action, though other cell membranes seem to be affected as well. Thus, Lonidamine inhibition of energy metabolism in nucleated cells reported in previous studies must be considered as a consequence of the structural damage of the inner and outer mitochondrial membranes, which in turn affects respiration and glycolysis and then cell viability.
Databáze: OpenAIRE