TY - JOUR
T1 - Liposomes modulate docetaxel-induced lipid oxidization and membrane damage in human hepatoma cells
AU - YANG, Zhijun
AU - FONG, David W F
AU - Yin, Linlin
AU - Wong, Yuenfan
AU - Huang, Wenhua
N1 - Funding Information:
The authors would like to thank Dr. Zhiling Yu (School of Chinese Medicine, Hong Kong Baptist University) for kindly providing HepG2 cells. This work was partially supported by a grant from Chia-Tai Tianqing Pharmaceutical Co., Ltd. (Nanjing, Jiangsu, China) Grant Number (JCTPCL/06/-06/01).
PY - 2009
Y1 - 2009
N2 - 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 IC50 values of 9.13×10-6±1.54×10 -5 and 1.58×10-2±2.71×10-2 mg/mL in HepG2 cells and SMMC-7721 cells, respectively, after of 24 hours of incubation. IC50 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.
AB - 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 IC50 values of 9.13×10-6±1.54×10 -5 and 1.58×10-2±2.71×10-2 mg/mL in HepG2 cells and SMMC-7721 cells, respectively, after of 24 hours of incubation. IC50 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.
KW - Docetaxel
KW - Hepatoma cell
KW - Liposome
KW - Membrane damage
KW - Oxidization
UR - http://www.scopus.com/inward/record.url?scp=70350614425&partnerID=8YFLogxK
U2 - 10.1080/08982100802632649
DO - 10.1080/08982100802632649
M3 - Journal article
C2 - 19235543
AN - SCOPUS:70350614425
SN - 0898-2104
VL - 19
SP - 122
EP - 130
JO - Journal of Liposome Research
JF - Journal of Liposome Research
IS - 2
ER -