Therapeutic effects of trehalose liposomes against lymphoblastic leukemia leading to apoptosis in vitro and in vivo

Abstract

Inhibitory effects of trehalose liposomes (DMTre) composed of 30mol% l-α-dimyristoylphosphatidylcholine (DMPC) and 70mol% trehalose surfactants on the growth of lymphoblastic leukemia (MOLT-4) cells in vitro and therapeutic effects of DMTre for xenograft mice model of carcinoma in vivo were examined. DMTre inhibited the growth of MOLT-4 cells in a dose-dependent manner due to apoptosis. The activation of caspase-3, -8, and 9 was obtained for MOLT-4 cells after the treatment with DMTre. The clustering of lipid rafts in plasma membranes of MOLT-4 cells was examined with a marker Cholera toxin subunit B conjugates Alexa Fluor (CTB), which binds to the pentasaccharide chains of ganglioside GM1 on the cellular surfaces. The clustering of lipid rafts in plasma membranes of MOLT-4 cells was observed after the treatment with DMTre. Therapeutic effects of DMTre were obtained for xenograft mice model of carcinoma in vivo.

Inhibitory Effects and Anti-Invasive Activities of Trehalose Liposomes on the Proliferation of Lung Carcinoma Cells

“…DMTreC14 were prepared using sonicator (VS-N300; VELVO, Tokyo, Japan) after the mixing DMPC (purity>99%; NOF Co. Ltd., Tokyo, Japan) and TreC14 (Dojindo Ltd., Kumamoto, Japan) in 5% glucose solution at 45°C with 300 W, and then filtrated with a 0.45 μm filter [7][8][9].…”

“…The diameter (d hy ) of DMTreC14 was measured by a light scattering spectrometer (ELS-8000, Otsuka Electronics, Osaka, Japan) using He −Ne laser (633 nm) at scattering angle=90° [7][8][9].…”

“…Cells were centrifuged and suspended in PBS (-) containing 1 mg/ml RNase, 0.1% Triton X-100 and 40 μg/ml propidium iodide (PI, Molecular Probes, Eugene, OR, USA) in a dark room. The percentage of apoptotic cells was analyzed using a flow cytometer (Epics XL system II, Beckman Coulter, Brea, CA, USA) [9].…”

“…The fusion and accumulation into the A549 cell membranes of DMTreC14 including a fluorescence probe (1-palmitoyl-2-[12-[(7-nitro-2-1,3-benzoxadiazol-4-yl)amino]-dodecanoyl]-sn-glycero-3-phosphocholine (NBDPC; Avanti Polar Lipids, Alabama, USA) was performed using confocal laser microscopy (TCS-SP; Leica Microsystems, Berlin, Germany) [7][8][9]. A549 cells (2.0 × 10 5 cells/ml) were incubated in a humidified incubator at 37°C and 5% CO 2 …”

“…Inhibitory effects of trehalose liposomes on the growth of tumor cells along with apoptosis have been reported [7][8][9]. Growth inhibition against colon, gastric, hepatocellular and leukemia cells has been obtained using trehalose liposomes without drugs.…”