The Effects Of 6-gingerol On Proliferation, Apoptosis Of Human Leukemia Molt4 Cells And K562 Cells

AIMS:To observe the effects of 6-gingerol on the acute T lymphocytic leukemia (ATLL) cell line Molt4 cells proliferation, apoptosis and other biological characteristics. To observe the influence of 6-gingerol combined with conventional antineoplastic on proliferation of Molt4 cells and K562 cells. To explore the anti-leukemia mechanisms of 6-gingerol,then to afford theory evidence for the clinical applications of those herb-extracted drugs with anti-keukemia.efficacy.METHODS:1. (1) Cell proliferation activity of Molt4 cells treated with 6-gingerol were measured by MTT assay; (2) Morphology changes of Molt4 cells of Hochest-33258 staining were observed by fluorescence microscope;(3) Inhibitory effects on cell cycles and early apoptosis rates of Molt4 cells treated with different concentrations of 6-gingerol were detected by flow cytometry; 4) Reactive oxygen species(ROS) levels of Molt4 cells treated with different concentrations of 6-gingerol were detected by flow cytometry; 2.Cell proliferation activity of 6-gingerol combined with Adriamycin(Adr) and cytrarabine(Ara-c) on the proliferation of Molt4 cells and K562 cells were measured by MTT assay.RESULTS:1.(1)6-Gingerol could inhibit the proliferation of Molt4 cells significantly after treated for 48,72 hours. Half inhibitory concentration(IC50) of 48, 72 hours were 19.4±0.2μg/ml,15.7±0.1μg/ml, respectively. The inhibitory rates were dosage and time-dependent;(2)Apoptotic Molt4 cells could be seen after treated with 6-gingerol for 48h. Early apoptosis rates in control group and DMSO group were 6.6%±0.2% and 7.0%±0.4%, respectively. Early apoptosis rates were 9.5%±0.3%, 15.0%±0.3% in 6-gingerol with 10μg/ml,15μg/ml concentration group respectively. Compared to two control groups, the early apoptosis rates significantly increased(p<0.01). The cell proportion of G1 stage in blank control group and DMSO control group were 37.5%±0.2%,39.6%±0.1%, respectively; of S stage were 50.6%±0.1%,51.6%±0.2%,respectively; of G2 stage were 11.7%±0.1%,8.7%±0.2%,respectively. While, the cell proportions of G1 stage in 6-gingerol with 20μg/ml,25μg/ml concentration group were 4.1%±0.1%,5.8%±0.1%, respectively; of, S stage were 85.1%±0.3%,87.1%±0.2%, respectively.respectively. It revealed that Molt4 cells were arrested in S stage(p<0.01),.(3)The mean fluorescence intensity (MIF) of blank control group and DMSO control group were 1016±28,1025±31, respectively. MFI in 6-gingerol 15μg/ml and 20μg/ml concentration group were 1282±24,1242±22, respectively. MIF increased significantly after treated with 6-gingerol(p<0.05).2.6-gingerol with different s (5μg/ml,10μg/ml) combined with Adriamycin(Adr) (0.5μg/ml,1μg/ml,2μg/ml),or 6-gingerol with 5μg/ml concentration combined with cytrarabine(Ara-c) (0.1μg/ml,0.2μg/ml,0.4μg/ml) could both afford synergic effects for Molt4 cells after treated for 48h.CONCLUSIONS:(1) 6-Gingerol could significantly inhibit the proliferation of Molt4cells, arrest cells in S stage. The mechanism might be inducing cell apoptosis and producing reactive oxygen free radicals.(2)6-Gingerol combined with Adriamycin(Adr) or cytrarabine(Ara-c) could both afford synergic effect for Molt4 cells.