Overexpression of human ether-à-go-go(eag) related gene(hERG) has been found in a broad range of human leukemia cell lines and primary human leukemia.The block of hERG protein might be a potential therapeutic strategy for leukemia.Gambogic acid(GA) has recently exhibited marked anti-tumor potency on solid tumors of various derivations.Here,we investigated the anti-leukemia effects of GA and its relation to the regulation of hERG in K562 leukemia cells in vitro.K562 cells were treated with various concentrations of GA(0.125-8.0 μmol/L) for 0-72 h.MTT assay was used to evaluate the inhibition effect of GA on the growth of K562 cells.Cell apoptosis was meas-ured through both Annexin-V FITC/PI double-labeled cytometry and transmission electron microscopy.Cell cycle regulation was studied by a propidium iodide method.RT-PCR and Western blot were applied to detect the expression level of hERG in K562 cells.GA presented striking growth inhibition and apoptosis induction potency on K562 cells in vitro in a time-and dose-dependent manner.The IC50 value of GA for 24 h was 2.637±0.208 μmol/L.Moreover,GA induced K562 cells arrested in G0/G1 phase,accordingly,cells in S phase decreased gradually,and no obvious changes were found in G2/M phase cells.Under the transmission electron microscopy,apoptotic bodies containing nuclear fragments were found in GA-treated K562 cells.After treatment with GA of 2.0 μmol/L for 24 h,the percentage of apoptotic cells was increased from 4.09% to 18.47%(P<0.01).Overexpression of hERG channel was found in K562 cells,while GA could down-regulate it at both protein and mRNA levels(P<0.01).It was concluded that GA exhibited its anti-leukemia effects partially through down-regulating the expression level of hERG channel in K562 cells,suggesting that GA may be a potential agent against leukemia with a mechanism of blocking hERG channel.
展开▼
