Hybrid liposomes can be prepared by simply ultrasonicating a mixture of vesicular and micellar molecules in aqueous solution. A clear solution of hybrid liposomes composed of 90 mol% dimyristoylphosphatidylcholine (DMPC) and 10 mol% polyoxyethylene(23)dodecyl ether (C-12(EO)(23)) having a hydrodynamic diameter of 100-120 urn was obtained. Highly inhibitory effects of hybrid liposomes of 90 mol% DMPC/10mol% C-12(EO)(23) on the growth of human lung carcinoma (RERF-LC-OK and A549) cells without any drugs were obtained. Induction of apoptosis by hybrid liposomes in RERF-LC-OK and A549 cells was verified on the basis of fluorescence microscopy, Agarose gel electrophoresis of DNA and flow cytometry. We elucidated the pathway of apoptosis induced by hybrid liposomes as follows: (a) accumulation of hybrid liposomes in tumor cell membrane was revealed using microphysiometer. (b) Reduction of mitochodrial membrane potential and activation of caspase-9, -3 and -8 were obtained, indicating that apoptotic signal by hybrid liposomes should pass through mitochondria and these caspases. It is worthy to note that such a novel mechanism of apoptosis induced by hybrid liposomes without any drugs was performed for the first time in human lung carcinoma cells. (c) 2004 Elsevier B.V. All rights reserved.