Inhibitory Effects of Hybrid Liposomes on the Growth of Tumor Cells along with Apoptosis Through the Activation of Caspases.

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We have produced hybrid liposomes (HL) which can be prepared by sonication of vesicular and micellar molecules in a buffer solution. The physical properties of HL such as size, shape, membrane fluidity, and the temperature of phase separation can be controlled by changing the constituents and compositional ratio.We examined the effects of HL composed of dimyristoylphosphatidylcholine (DMPC) and 10mol% polyoxyethylenedodecyl ether (C_<12>(EO)_<23>) on the growth of human colon tumor cells (WiDr). It is worthy to note that a good correlation between the P values of 1,6-diphenyl-1,3,5-hecatriene incorporated into HL and fifty percent inhibitory concentration (IC_<50>) was obtained. This indicates that HL having larger fluidity could suppress greater the growth of tumor cells. HL distinguished between WiDr tumor cells and normal colon cells and then fused and accumulated into the membranes of WiDr cells leading to apoptosis. Activation of caspase-8,-9, and-3 was observed for WiDr cells after the treatment with HL, indicating that HL could apoptosis through the activation of caspase-8,-9, and-3. This study demonstrated that growth inhibition and apoptosis for tumor cells by HL provides the possibility of therapy from a viewpoint biophysical characteristics of tumor cell membrane.Highly inhibitory effects of HL on the growth of human breast tumor cells in vitro were obtained. Induction of apoptosis through the activation of caspases by HL was clearly obtained.HL induced apoptosis for human lymphoma cells in vitro. No toxicity was observed in the rats after intravenously injecting HL in vivo. We clearly demonstrated that a mouse model of lymphoma was established and prolonged survival was obtained in mice model of lymphoma after the treatment with HL without drugs in vivo.