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

Yuji Komizu, Hidetsugu Ueoka, Koichi Goto, Ryuichi UeokaDivision of Applied Life Science, Graduate School of Engineering, Sojo University, Ikeda, Kumamoto, JapanBackground: Hybrid liposomes can be prepared by simply sonicating a mixture of vesicular and micellar molecules in buffer solutions. In this study, we investigated the effects of hybrid liposomes on the growth of human colon cancer cells in vitro.Methods: Hybrid liposomes (HL-n, n = 21, 23, 25) composed of L-α-dimyristoylphosphatidylcholine (DMPC) and polyoxyethylene(n) dodecyl ethers (C12(EO)n, n = 21, 23, 25) were prepared by the sonication method and their inhibitory effects on growth of human colon cancer HCT116 cells were examined in vitro.Results: Significant growth inhibition of HCT116 cells was observed in the presence of HL-n. The fifty percent inhibitory concentration (IC50) of HL-n was less than half that of DMPC liposomes. Furthermore, fluorescence microscopic and flow cytometric analyses indicated that the markedly inhibitory effects of HL-n on the growth of HCT116 cells could be attained through the induction of cell cycle arrest at the G0/G1 phase along with apoptotic cell death.Conclusion: It was found for the first time that HL-n can induce both cell cycle arrest and apoptosis in colon cancer cells. The findings in this study should contribute to novel chemotherapy for colon cancer.Keywords: hybrid liposome, colon cancer cell, cell cycle arrest, apoptosi

Consideration of Commercially Available Hepatocytes as Cell Sources for Liver-Microphysiological Systems by Comparing Liver Characteristics

In recent years, microphysiological systems (MPS) have been developed to shorten the test period and reduce animal experiments for drug development. We examined cell sources for the liver-MPS, i.e., MPS mimicking liver function. For liver-MPS, liver-like cells with high liver functions are required. Cryo-preserved hepatocytes (cryoheps), the gold standard hepatocytes for in vitro drug development, present several disadvantages, including differences between lots due to individual donor variations or a limited cell supply from the same donor. As such, alternatives for cryoheps are sought. Hepatocyte-like cells derived from human induced pluripotent stem cells (hiPSC-Heps), hepatocytes derived from liver-humanized mice (PXB-cells), and human liver cancer cells (HepG2 cells) were examined as source candidates for liver-MPS. Gene expression levels of the major cytochrome P450 of hiPSC-Heps, PXB cells, and HepG2 cells were compared with 22 lots of cryoheps, and the activities of hiPSC-Heps were compared with 8 lots of cryopreserved hepatocytes. A focused DNA microarray was used for the global gene analysis of the liver-like characteristics of hiPSC-Heps, PXB-cells, cryoheps, and HepG2 cells. Gene expression data from the focused microarray were analyzed by principal component analysis, hierarchical clustering, and enrichment analysis. The results indicated the characteristics of individual hepatocyte cell source and raised their consideration points as an alternative cell source candidate for liver-MPS. The study contributes to the repetitive utilization of a robust in vitro hepatic assay system over long periods with stable functionality

The accuracy of reconstruction techniques for determining hybrid rocket fuel regression rate

This study is an investigation of the accuracy of reconstruction techniques for determining instantaneous fuel regression rate. Results of reconstruction techniques are compared with results obtained through the measurement of the pressure drop across the fuel in an Axial-Injection End-Burning hybrid rocket (EBHR). The results of numerous firing tests show that this method allows for the evaluation of the accuracy of the instantaneous fuel regression rates obtained by reconstruction techniques. The error bias of O/F values calculated by the reconstruction techniques were around ±10%, and were mainly caused by uncertainties in the measured values of oxidizer mass flowrate and the definition of firing duration. The instantaneous length of an EBHR-type fuel can be calculated from the measurement of the pressure drop across the fuel. However, the calculated fuel length history obtained by the pressure drop in a port does not coincide with that obtained by the reconstruction technique because of an underestimation in pressure drop