The in vitro inhibitory activity of Lonidamine on the aerobic glycolysis of normal as well as leukemic lymphocytes has been investigated. The extent of the impairment of lactate production induced by Lonidamine on normal thymus (T)- and bone marrow (B)-derived lymphocytes was found to be dependent on their source of origin, i.e. residing or circulating pool. Among leukemia tested ‘null’ and B cell leukemias appeared the most affected metabolically by the compound. Administration in vivo of the drug to the patient with B cell chronic leukemia resulted in a decrease of lactate production by leukemic cells comparable to that induced in vitro. These metabolic changes were paralleled in normal, as well as in leukemic cells by ultrastruc-tural lesions, mainly confined to the mitochondrial compartment.

Lonidamine induces in murine and human tumor cells severe morphological damage of the mitochondria and other cytoplasmic structures both ‘in vitro’ and ‘in vivo’. Biochemical studies have demonstrated that the drug decreases oxygen consumption and lactate production. The sensitivity of human tumor cells is not related to their histotype. Lonidamine’s effects on mitochondria, glycolysis, pentose phosphate pathway, and aromatase activity are discussed.