[Effect of cytochrome CYP2C19 on the anti-myeloma activity of thalidomide in vitro].
OBJECTIVE
To investigate the effect of human liver microsome on anti-myeloma activity of thalidomide (TH) in vitro and identify the role of cytochrome CYP2C19 in it.


METHODS
Human multiple myeloma (MM) cell lines U266, NCI-H929, RPMI 8226, LP-1 and CZ-1 were treated with TH or TH pre-incubated with human liver microsome. Cell viability was detected by MTT assay, and cell cycle and apoptosis by flow cytometry (FCM).


RESULTS
TH treatment had no direct effect on cell viability at concentrations of 10 microg/ml, 50 microg/ml and 100 microg/ml, the viabilities of the 5 MM cell lines were 96.2% - 103.7%, 96.3% - 103.7% and 97.9% - 106.5% respectively, being no significant difference from that of control (P > 0.05). However, when preincubated with human liver microsome, TH significantly inhibited the cell viability with a dose-dependent manner. At concentrations of 10 microg/ml, 50 microg/ml and 100 microg/ml, TH pre-incubated with human liver microsome led to 12.2% - 22.9%, 25.9% - 36.4% and 34.9% - 46.3% decreases of cell viability, respectively (P < 0.05). TH at concentration of 100 microg/ml pre-incubated with human liver microsome caused an increase of 18.5% - 32.5% in apoptosis cells. When omeprazole, a specific inhibitor of cytochrome CYP2C19, was added in the incubation system, the inhibition of cell viability by TH was weakened. At concentrations of 5 micromol/L and 10 micromol/L, omeprazole reversed the cell viability by 7.5% - 21.9% and 19.1% - 38.3%, respectively (P < 0.05).


CONCLUSIONS
Treatment of TH with human liver microsome is essential for its anti-myeloma activity in vitro, and cytochrome CYP2C19 is involved with this metabolism process.
Li
Yong-Hua
YH
Department of Hematology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China.
Hou
Jian
J
Jiang
Hua
H
Huang
Hong-Ming
HM
Zhu
Rong
R
D017209:Apoptosis / Q000187:drug effects; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D065731:Cytochrome P-450 CYP2C19; D006801:Humans; D008862:Microsomes, Liver / Q000378:metabolism; D009101:Multiple Myeloma / Q000378:metabolism / Q000473:pathology*; D013792:Thalidomide / Q000494:pharmacology*
D013792:Thalidomide; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19