Curcumin inhibits WT1 gene expression in human leukemic K562 cells

来源 :Acta Pharmacologica Sinica | 被引量 : 0次 | 上传用户:wangxin3163
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Aim:Wilms’ tumorl(WT1)gene is highly expressed in leukemic blast cells ofmyeloid and lymphoid origin.Thus,WTI mRNA and protein serve as promisingtumor markers for the detection of leukemia and monitoring of disease progression.The purpose of this study was to investigate the modulating effects of curcuminon WTI gene expression in the human leukemic cell line K562.Methods:Thecytotoxicity of curcumin on the K562 cell line was evaluated by using 3-(4,5-dimethyl-2 thiazoyl)-2,5-diphenyl-tetrazolium bromide(MTT)assay.The K562cell line was treated with a non-cytptoxic dose of curcumin(5,10,or 15 μmol/L) for13 d.The expression levels of WT1 protein and WT1 mRNA were assessed byWestern blot analysis and reverse transcription-polymerase chain reaction(RT-PCR),respectively.Results:Curcumin had a cytotoxic effect on K562 leukemiccells with an inhibitory concentration at 50%(IC_(50)) of approximately 20 μg/mL(54.3 μmol/L).Non-cytotoxic doses of curcumin,at concentrations of 5,10,and 15pmol/L for 2 d,decreased the level of WT1 protein and WT1 mRNA in the K562cell line in a dose-dependent manner.Similarly,curcumin at a concentration of 10μmol/L significantly decreased the level of WT1 protein and mRNA in a time-dependent manner.Conclusion:The inhibitory effects of curcumin are associ-ated with a decrease in the levels of both WT1 protein and WT1 mRNA.Thecurrent study provides a molecular basis for future clinical trials in leukemic patients.Thus,curcumin could be a promising chemotherapeutic agent for human leukemia. Aim: Wilms’ tumorl (WT1) gene is highly expressed in leukemic blast cells of myeloid and lymphoid origin. Thus, WTI mRNA and protein serve as promising tumor markers for the detection of leukemia and monitoring of disease progression. The purpose of this study was to investigate the modulating effects of curcuminon WTI gene expression in the human leukemic cell line K562. Methods: The cytotoxicity of curcumin on the K562 cell line was evaluated by using 3- (4,5-dimethyl-2 thiazoyl) -2,5-diphenyl-tetrazolium (MTT) assay. The K562 cell line was treated with a non-cytotoxic dose of curcumin (5, 10, or 15 μmol / L) for 13 days. The expression levels of WT1 protein and WT1 mRNA were assessed by Western blot analysis and reverse transcription Results: Curcumin had a cytotoxic effect on K562 leukemic cells with an inhibitory concentration at 50% (IC_ (50)) of approximately 20 μg / mL (54.3 μmol / L) cytotoxic doses of curcumin, at concentrations of 5, 10, and 15 pmol / L fo r2 d, decreased the level of WT1 protein and WT1 mRNA in the dose-dependent manner of K562cell line. Similarly, curcumin at a concentration of 10 μmol / L significantly decreased the level of WT1 protein and mRNA in a time-dependent manner. Conclusion: The inhibitory effects of curcumin are associ-ated with a decrease in the levels of both WT1 protein and WT1 mRNA. The current study provides a molecular basis for future clinical trials in leukemic patients. Thus, curcumin could be a promising chemotherapeutic agent for human leukemia.
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