Novel mechanism of hybrid liposomes‐induced apoptosis in human tumor cells

Abstract

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. ' 2005 Wiley-Liss, Inc.

Remarkable inhibitory effects of hybrid liposomes on growth of human colon cancer cells through induction of cell cycle arrest along with apoptosis

“…16,17 Hybrid liposomes being more fluid as compared with DMPC liposomes showed strong inhibitory effects on the growth of human colon cancer (WiDr) cells 16 and human leukemia cells. 12 The strong inhibitory effects on the growth of HCT116 cells should be closely related to the membrane fluidity of HL-n.…”

“…It has been already elucidated that hybrid liposomes induce apoptosis in various tumor cells, with activations of caspases-3, -8, and -9, and reduction of mitochondria membrane potential. 8,[11][12][13]16 HL-n could probably fuse and accumulate into HCT116 cells, and induce apoptosis through activation of caspase cascades.…”

“…5 On the other hand, hybrid liposomes composed of DMPC and polyoxyethylene(n) alkyl ethers without any drugs demonstrated remarkable inhibitory effects on the growth of various tumor cells in vitro [6][7][8] and in vivo. [9][10][11][12] In addition, it has been demonstrated that hybrid liposomes could induce apoptotic cell death in leukemia, 13 hepatoma, 7 lung cancer, 14 breast cancer, 8 and primary effusion lymphoma cells. 15 With respect to colon cancer cell lines, hybrid liposomes induced apoptosis in human colon adenocarcinoma WiDr 16 and mouse colon carcinoma Colon26 cells in vitro.…”

Apoptotic and Anti-invasive Effects of Hybrid Liposomes without Drugs against Human Breast Cancer Cells In Vitro

“…Studies of HL made of DMPC and polyoxyethylene (n) dodecyl ethers (C 12 (EO) n ) on the in vitro [7][8][9] and in vivo [9][10][11][12] development of lymphoma cells, and clinical applications [12] without drugs have already been reported. In chemotherapy for HER2-negative breast cancer, invasive suppression and the apoptotic induction of breast cancer cell are important treatment strategies.…”

Specific Interaction between Ca2+ and Anionic Lipids in Cancer Cells along with Apoptosis

“…5) With respect to the role of Ca 2ϩ in inhibition of cellular proliferation, it has been reported that Ca 2ϩ imported into the cytoplasm of mammalian cells could lead to a programmed cell death "apoptosis" through several signalling pathways. 6,7) However, the mechanistic details of tumor-specific growth inhibition effects of Ca On the other hand, we have investigated the membrane targeted chemotherapy with hybrid liposomes 8,9) composed of phospholipids and nonionic surfactants for tumor cells in vitro, [10][11][12][13][14][15] in vivo, 15,16) and in clinical applications. 16,17) Significantly, the denaturation of cell membranes by hybrid liposomes could lead to apoptosis in tumor cells without any drugs.…”