Title : Therapeutic effects of trehalose liposomes against tumors along with apoptosis
Abstract:
Trehalose stabilizes membranes and proteins in cells most likely by hydrogen bonding. Trehalose liposomes (DMTre) composed of L-α-dimyristoylphosphatidylcholine (DMPC) and trehalose micelles (TreC14) have been produced by sonication of a mixture of DMPC and TreC14 in a buffer solution with no organic solvent. The remarkable inhibitory effects of DMTre on the growth of human colon, gastric, hepatocellular, and lymphobrastic carcinoma cells have been reported. In this study, we investigated inhibitory effects of DMTre against breast cancer and lung carcinoma. Hydrodynamic diameter (dhy) of DMTre composed of 30 mol% DMPC and 70 mol% TreC14 was 100 nm with single and narrow range of size distribution, which can avoid reticular endotherial system in vivo. The thickness of the fixed aqueous layer (TFAL) of DMTreCn was evaluated from the zeta potential and increase in TFAL values of DMTreCn was obtained in a dose-dependent manner.1 The TFAL values for DMTreCn were larger than that of DMPC liposomes. DMTre inhibited the growth of breast tumor (MCF-7 and MDA-MB-453) cells leading to apoptosis with the activation of caspases. The suppression of tumor weight of xenograft mice model of carcinoma treated with DMTre after inoculation with breast tumor cells was obtained along with apoptosis. The remarkable reducton of volume and weight in subcutaneous tumors on subcutaneous lung carcinoma-bearing mice administered with DMTre were obtained. Dimensions of tumor area of lung on the orthotopic graft-bearing mice of lung carcinoma significantly decreased after the administration with DMTre.
