ABSTRACT
OBJECTIVE@#To investigate the effects of dihydroartemisinin (DHA) on the proliferation and apoptosis of human T-cell acute lymphoblastic leukemia (T-ALL) Jurkat cell.@*METHODS@#The effects of DHA on the proliferation of Jurkat cells and the recovery of DHA-inhibited cell viability by N-acetyl-L-cysteine (NAC) were examined by CCK-8 assay. Flow cytometry was performed to analyze the cell apoptosis and generation of reactive oxygen species (ROS). Western-blot was used to detected protein expression of DNA damage-related genes, as well as apoptosis-associated genes, respectively.@*RESULTS@#DHA inhibited the proliferation of Jurkat cells, and shows a concentration-dependent manner(r =0.936), and NAC could partially restore the activity of DHA on cell proliferation inhibition. With the increase of drug concentration, the apoptosis rate (r =0.946) and ROS accumulation was increased (r =0.965). Western blot showed that the protein expressions of DNA damage-related gene γ-H2AX and apoptosis-related genes p53, c-Caspase3, BAX and cPARP were significantly increased, and BCL-2 protein expression was decreased.@*CONCLUSION@#DHA can induce ROS production in Jurkat cells, which can cause DNA damage, activate the P53 apoptotic pathway, and promote apoptosis of cells.
Subject(s)
Humans , Apoptosis , Artemisinins , Jurkat Cells , Oxidative Stress , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma , Reactive Oxygen SpeciesABSTRACT
OBJECTIVE@#To study the effects of dihydroartemisinin (DHA) on the proliferation and apoptosis of acute myeloid leukemia (AML) cells.@*METHODS@#The effects of DHA on the proliferation of acute myeloid leukemia cells and the inhibitory effect of Z-VAD-FMK on the DHA-induced cell apoptosis were detected by CCK-8 assay. The expression level of cleaved-caspased 3 was detected by indirect immunofluorescence. Western blot was used to quantify the protein expression of PTEN, p-Akt, AKT, β-actin, and the apoptosis-associated proteins, such as C-PARP, Cleaved-caspase3 and Caspase3 respectively.@*RESULTS@#DHA induced the AML cell apoptosis with concentration-dependent manner (r=-0.959, r=-0.956). The DHA could induce the accumulation of cleaved-caspase 3 and C-PARP in AML cells, activate PTEN gene and inhibited Akt phosphorylation. Apoptosis inhibitor Z-VAD-FMK could partially restored the activity of DHA-inhibited cell proliferation.@*CONCLUSION@#Dihydroartemisinin induces AML cell apoptosis by inhibition of PTEN/AKT pathway. Dihydroartemisinin is expected to be a safe and effective drug for treatment of acute myeloid leukemia.
ABSTRACT
OBJECTIVE@#To investigate the effect of sorafenib combined with decitabine on the viability and apoptosis of diffuse large B-cell lymphoma cell line OCI-LY1 and its mechanism.@*METHODS@#Sorafenib at 1.5μmol/L or decitabine at 25μmol/L was used to treat the cells alone or in combination. The viability of OCI-LY1 cells was detected by CCK8 assay; the PI positive cells were observed by fluorescence microscopy; the cell proliferation and ROS levels were measured by flow cytometry; The expression levels of proteins related to apoptosis were detected by Western blot.@*RESULTS@#Compared with the control group, treatment with sorafenib and decitabine alone or in combination inhibited the cell proliferation, activated ROS formation and induced apoptosis finally. Sorafenib in combination with decitabine produced a synergistic effect. Western blot analysis showed that sorafenib combined with decitabine significantly up-regulated the levels of Bax/Bcl-2, P53, C-Caspase3 and C-PARP and activated apoptosis by inhibiting PI3K-AKT pathway.@*CONCLUSION@#Sorafenib combined with decitabine induces the apoptosis of diffuse large B-cell lymphoma cell line OCI-LY1 by inhibiting PI3K-AKT pathway and activating P53.