Novel mechanism of hybrid liposomes-induced apoptosis in human tumor cells.
Hybrid liposomes can be prepared by simply ultrasonicating a mixture of vesicular and micellar molecules in a buffer solution. The physical properties of these liposomes, such as size, membrane fluidity, phase transition temperature and hydrophobicity can be controlled by changing the composition. Hybrid liposomes composed of dimyristoylphosphatidylcholine and polyoxyethylene (10) dodecyl ether were found to inhibit the growth of human promyelocytic leukemia (HL-60) cells without using any drugs. Induction of apoptosis by hybrid liposomes in HL-60 cells was verified on the basis of fluorescence microscopy and flow cytometry analysis, after fusion and accumulation of hybrid liposomes, which was revealed on the basis of microphysiometer. We elucidated the pathways of apoptosis induced by the hybrid liposomes. That is, hybrid liposomes fused and accumulated in tumor cell membranes, and the apoptosis signal first passed through mitochondria, caspase-9 and caspase-3, second through Fas, caspase-8, caspase-3 and then reached the nucleus. Hybrid liposomes themselves can induce apoptosis in human tumor cells along with high inhibitory effects on the growth of tumor cells.
Matsumoto
Yoko
Y
Graduate Course of Applied Chemistry, Sojo University, Ikeda, Kumamoto, Japan.
Iwamoto
Yasunori
Y
Matsushita
Taku
T
Ueoka
Ryuichi
R
D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D053418:Death Domain Receptor Signaling Adaptor Proteins; D004134:Dimyristoylphosphatidylcholine / Q000378:metabolism / Q000494:pharmacology*; D018922:HL-60 Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007202:Indicators and Reagents / Q000378:metabolism / Q000494:pharmacology; D008081:Liposomes / Q000378:metabolism / Q000494:pharmacology*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D000077423:Polidocanol; D011092:Polyethylene Glycols / Q000378:metabolism / Q000494:pharmacology*; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism
D000970:Antineoplastic Agents; D053418:Death Domain Receptor Signaling Adaptor Proteins; D007202:Indicators and Reagents; D008081:Liposomes; D018124:Receptors, Tumor Necrosis Factor; D000077423:Polidocanol; D011092:Polyethylene Glycols; D045304:Cytochromes c; C505407:CASP3 protein, human; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases; D004134:Dimyristoylphosphatidylcholine