Teniposide-induced changes in the physical properties of phosphatidylcholine liposomes. A calorimetric study

The anticancer agent teniposide has significant effects on plasma membrane components, in addition to its well known nuclear effects. Alterations in the properties and function of cellular membranes by various amphipathic compounds have been attributed previously to their relatively non-specific interactions with membrane components. We have examined the interaction of teniposide with defined model membranes by monitoring drug-induced changes in the melting profile of phospholipids by differential scanning calorimetry. The main phase transition temperature of dimyristoyl- or dipalmitoylphosphatidylcholine was lowered and broadened by the presence of teniposide in the liposomes. These effects were essentially linear over the concentration range of 1-5 mole %. The calorimetric enthalpy of the gel to liquid-crystalline transition of the phospholipids was not changed by the addition of the drug. The characteristic pretransition of these saturated phospholipids was decreased by teniposide concentrations as low as 0.1 mole % and was abolished at teniposide concentrations greater than 1 mole %. The data confirm the lipophilic nature of teniposide and indicate that the non-specific interactions with membrane lipids should be considered when evaluating the membrane-related effects of this agent.