title: Liposomes modulate docetaxel-induced lipid oxidization and membrane damage in human hepatoma cells.
abstract: The aim of this study was to investigate the effect of liposomes on docetaxel-induced lipid oxidization and membrane damage in human hepatoma cells. Cytotoxicity of free docetaxel and docetaxel-containing liposomes was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) assay in human hepatoma cell lines HepG2 and SMMC-7721. To the cell lines, blank liposomes prepared with soybean phosphatidylcholine (SPC), dimyristoylphosphocholine (DMPC), and dioleoylphosphocholine (DOPC) did not show any significant toxicity below a 0.02-mg/mL phospholipid concentration. On the other hand, free docetaxel showed IC(50) values of 9.13 x 10(-6) +/- 1.54 x 10(-5) and 1.58 x 10(-2) +/- 2.71 x 10(-2) mg/mL in HepG2 cells and SMMC-7721 cells, respectively, after of 24 hours of incubation. IC(50) values of docetaxel-encapsulating liposomes, measured in terms of total docetaxel concentration, were at least 1.5-fold higher than those of free docetaxel. SPC liposomes reduced cellular damage caused by free docetaxel, as evidenced by the attenuation of docetaxel-induced lactate dehydrogenase (LDH) leakage by over 11% after liposome encapsulation at each dosage. Docetaxel-induced oxidative membrane damage was monitored by the formation of the lipid peroxidation product, malondialdehyde (MDA), and the antioxidative property of SPC liposome was monitored by the suppression of superoxide dismutase (SOD). These data demonstrated that free docetaxel facilitated MDA formation and suppressed SOD, and that these membrane-damaging effects were reduced by SPC liposomes.
authors.affiliation: School of Chinese Medicine, Hong Kong Baptist University, 7 Baptist University Road, Hong Kong, China. yzhijun@hkbu.edu.hk
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Yang
authors.forename: David W F
authors.initials: DW
authors.lastname: Fong
authors.forename: Linlin
authors.initials: L
authors.lastname: Yin
authors.forename: Yuenfan
authors.initials: Y
authors.lastname: Wong
authors.forename: Wenhua
authors.initials: W
authors.lastname: Huang
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000378:metabolism; D000077143:Docetaxel; D056945:Hep G2 Cells; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects; D008055:Lipids / Q000494:pharmacology; D008081:Liposomes / Q000378:metabolism* / Q000494:pharmacology; D008113:Liver Neoplasms / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism / Q000494:pharmacology; D008566:Membranes / Q000378:metabolism; D010084:Oxidation-Reduction; D013482:Superoxide Dismutase / Q000378:metabolism / Q000494:pharmacology; D043823:Taxoids
chemical_list: D008055:Lipids; D008081:Liposomes; D043823:Taxoids; D000077143:Docetaxel; D008315:Malondialdehyde; D007770:L-Lactate Dehydrogenase; D013482:Superoxide Dismutase