scholarly journals Knockdown of DGKZ induces apoptosis and G2/M phase arrest in human acute myeloid leukemia HL-60 cells

2018 ◽  
Author(s):  
Changhu Dong ◽  
Hong Li ◽  
Yanning Tian ◽  
Xiang Li ◽  
Bing Wang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Acute Myeloid Leukemia ◽  
Western Blot ◽  
Myeloid Leukemia ◽  
Cell Counting ◽  
Cycle Phase ◽  
Cycle Arrest ◽  
M Phase ◽  
Human Acute Myeloid Leukemia ◽  
Acute Myeloid

AbstractDiacylglycerol kinase zeta (DGKZ) is associated with the pathogenesis of a variety of malignant diseases, but its biological function on acute myeloid leukemia (AML) has not been explored. This study was aimed to analyze apoptosis induced by Knockdown of DGKZ and its mechanism in human acute myeloid leukemia HL-60 cells.In the present study qRT-PCR was used to detect the expression of DGKZ in HL-60, THP-1, K562, H9, Jurkat and CD34 cell lines. DGKZ-shRNA lentiviral vector was established and used to infect acute myeloid leukemia HL-60 cells. Cell Counting Kit-8 (CCK-8) assay was used to determine the viability of HL-60 cells DGKZ knocked down. Apoptosis and cell cycle phase of HL-60 cells after DGKZ knockdown were evaluated by flow cytometry. Western blot analysis was performed to investigated the protein expression related to apoptosis and cell cycle. Results showed DGKZ expression were stable and higher in Jurkat, HL-60, THP-1,K562 leukemia cells than those of H9 and CD34 cells. Compared with cells of the shCtrl group, DGKZ was markedly knocked down in cells which were transfected with lentivirus encoding shRNA of DGKZ in HL-60 cells. DGKZ knockdown significantly inhibited the proliferation and induced cycle arrest at the G2/M phase in HL-60 cells. Western blot results indicated the expressions of caspase-3, caspase-8, and survivin markedly increased in HL-60 cells after knockdown of DGKZ. The results suggest Knockdown of DGKZ can inhibit proliferation of acute myeloid leukemia HL-60 cell caused cell cycle arrest at the G2/M phase through caspases pathway.

scholarly journals Axolotl Ambystoma mexicanum extract induces cell cycle arrest and differentiation in human acute myeloid leukemia HL-60 cells

Tumor Biology ◽  
2020 ◽  
Vol 42 (9) ◽  
pp. 101042832095473
Author(s):  
Sherif Suleiman ◽  
Riccardo Di Fiore ◽  
Analisse Cassar ◽  
Melissa Marie Formosa ◽  
Pierre Schembri-Wismayer ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Acute Myeloid Leukemia ◽  
Anticancer Activity ◽  
Cell Cycle Arrest ◽  
Crude Extract ◽  
Myeloid Leukemia ◽  
Ambystoma Mexicanum ◽  
Cycle Arrest ◽  
Human Acute Myeloid Leukemia ◽  
Acute Myeloid

Acute myeloid leukemia is the most common form of acute leukemia in adults, constituting about 80% of cases. Although remarkable progress has been made in the therapeutic scenario for patients with acute myeloid leukemia, research and development of new and effective anticancer agents to improve patient outcome and minimize toxicity is needed. In this study, the antitumor activity of axolotl (AXO) Ambystoma mexicanum crude extract was assessed in vitro on the human acute myeloid leukemia HL-60 cell line. The anticancer activity was evaluated in terms of ability to influence proliferative activity, cell viability, cell cycle arrest, and differentiation. Moreover, gene expression analysis was performed to evaluate the genes involved in the regulation of these processes. The AXO crude extract exhibited antiproliferative but not cytotoxic activities on HL-60 cells, with cell cycle arrest in the G0/G1 phase. Furthermore, the AXO-treated HL-60 cells showed an increase in both the percentage of nitroblue tetrazolium positive cells and the expression of CD11b, whereas the proportion of CD14-positive cells did not change, suggesting that extract is able to induce differentiation toward the granulocytic lineage. Finally, the treatment with AXO extract caused upregulation of CEBPA, CEBPB, CEBPE, SPI1, CDKN1A, and CDKN2C, and downregulation of c-MYC. Our data clearly show the potential anticancer activity of Ambystoma mexicanum on HL-60 cells and suggest that it could help develop promising therapeutic agents for the treatment of acute myeloid leukemia.

Dentatin Induces Apoptosis and Cell Cycle Arrest of Acute Myeloid Leukemia Cells

2020 ◽  
Vol 19 (1) ◽  
pp. 52-57
Author(s):  
Li Wen ◽  
Yuli Liang ◽  
Jing Li ◽  
Meijie Quan ◽  
Yanxiao Li ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Acute Myeloid Leukemia ◽  
Cell Viability ◽  
Cell Apoptosis ◽  
Myeloid Leukemia ◽  
Cell Counting ◽  
Dependent Manner ◽  
Cycle Arrest ◽  
Acute Myeloid Leukemia Cells ◽  
Acute Myeloid

Acute myeloid leukemia remains a therapeutic challenge in the medical field and improvement in chemotherapeutics is needed. In this paper, MOLM-13 cells were treated with different concentrations (0, 10, 50, 100 µM) of dentatin and cell viability was detected using Cell Counting Kit-8. Cell cycle and cell apoptosis rates were evaluated by flow cytometry. The relevant proteins were assessed by Western blot. Consequently, the results show that dentatin inhibits the cell viability in a dose-dependent manner. In addition, dentatin arrests the cell cycle at G1 phase (P ‹ 0.01). Moreover, dentatin induces the cell apoptosis. Further study revealed that dentatin downregulates the phosphorylated STAT3 and CyclinD1 but upregulates the cleaved caspase-3. In summary, this study confirms that dentatin inhibits MOLM-13 cell viability, increases cell apoptosis, and retards cell cycle.

Octadecyloxyethyl Adefovir Exhibits Potent in vitro and in vivo Cytotoxic Activity and Has Synergistic Effects with Ara-C in Acute Myeloid Leukemia

Chemotherapy ◽  
2018 ◽  
Vol 63 (4) ◽  
pp. 225-237 ◽  
Author(s):  
Haytham Khoury ◽  
Ruijuan He ◽  
Aaron Schimmer ◽  
James R. Beadle ◽  
Karl Y. Hostetler ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Acute Myeloid Leukemia ◽  
Cell Cycle Arrest ◽  
Clinical Benefit ◽  
Myeloid Leukemia ◽  
Mouse Bone Marrow ◽  
Medical Needs ◽  
Cycle Arrest ◽  
Acute Myeloid

Acute myeloid leukemia (AML) continues to be a deadly disease, with only 50–70% of patients achieving complete remission and less than 30% of adults having sustained long-term remissions. In order to address these unmet medical needs, we carried out a high-throughput screen of an in-house library of on- and off-patent drugs with the OCI/AML-2 cell line. Through this screen, we discovered adefovir dipi­voxil (adefovir-DP) as being active against human AML. In addition to adefovir-DP, there are second-generation formulations of adefovir, including octadecyloxyethyl adefovir (ODE-adefovir) and hexadecyloxypropyl adefovir (HDP-adefovir), which were designed to overcome the pharmacokinetic problems of the parent compound adefovir. Given the known clinical benefit of nucleoside analogs for the treatment of AML, we undertook studies to evaluate the potential benefit of adefovir-based molecules. In AML cell lines and patient samples, adefovir-DP and ODE-adefovir were highly potent, whereas HDP-adefovir was significantly less active. Interestingly, ODE-adefovir was remarkably less toxic than adefovir-DP towards normal hematopoietic cells. In addition, ODE-adefovir at a dose of 15 mg/kg/day showed potent activity against human AML in a NOD/SCID mouse model, with a reduction of human leukemia in mouse bone marrow of > 40% in all mice tested within 20 days of treatment. Based on its chemical structure, we hypothesized that the cytotoxicity of ODE-adefovir toward AML was through cell cycle arrest and DNA damage. Indeed, ODE-adefovir treatment induced cell cycle arrest in the S phase and increased levels of pH2Ax, indicating the induction of DNA damage. Furthermore, there was an increase in phospho-p53, transactivation of proapoptotic genes and activation of the intrinsic apoptotic pathway. Subsequent investigation unveiled strong synergism between ODE-adefovir and ara-C, making their coadministration of potential clinical benefit. Expression of MRP4, a nucleoside transporter, appeared to influence the response of AML cells to ODE-adefovir, as its inhibition potentiated ODE-adefovir killing. Taken together, our findings indicate that clinical development of ODE-adefovir or related compounds for the treatment of AML is warranted.

G1 Cell-Cycle Arrest and Apoptosis by Histone Deacetylase Inhibition in MLL-AF9 Acute Myeloid Leukemia Cells Is MLL-AF9 Independent.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4410-4410
Author(s):  
Roberto Tonelli ◽  
Roberta Sartini ◽  
Raffaele Fronza ◽  
Francesca Freccero ◽  
Monica Franzoni ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Acute Myeloid Leukemia ◽  
Cell Growth ◽  
Cell Cycle Arrest ◽  
Myeloid Leukemia ◽  
Combined Treatment ◽  
Histone Deacetylase Inhibition ◽  
Cycle Arrest ◽  
G1 Cell Cycle Arrest ◽  
Acute Myeloid

Abstract Acute myeloid leukemia (AML) with MLL rearrangements (MLLmut), found mainly in M5 or M4 FAB subtypes, is frequent in infants and secondary leukemias. The most common MLL translocation gives rise to MLL-AF9. MLL protein interacts with histone deacetylases (HDACs) -1 and -2 through the MLL repression domain. We report the effects of HDAC inhibition by valproic acid (VPA) in MLL-AF9 AML-M5 cells (THP-1, MM6 and MOLM-13) and MLLmut AML-M5 blasts. VPA led to histone hyper-acetylation, strong cell-growth inhibition, G1 cell-cycle arrest and apoptosis. Combined treatment with all-trans-retinoic-acid (ATRA) did not substantially improve these effects. VPA increased MLL-AF9 transcription, indicating that VPA overcomes the cell-growth promoting activity and resistance to apoptosis conferred by MLL-AF9 in AML-M5 cells, even with increased MLL-AF9. A small number of genes were significantly affected by VPA in p53-absent THP-1 cells (GeneChip analysis), and the majority of these were up-regulated. VPA potently induced p21 and cyclin G2 (CG2) expression. p21 and CG2 targeted inhibition demonstrated that p21 acts as a key regulator in the VPA-inducted G1 cell-cycle arrest, while induction of CG2 has no effect. These data suggest that these poor prognosis patients may benefit from HDAC inhibitor therapy.

scholarly journals Curcumin promotes cell cycle arrest and apoptosis of acute myeloid leukemia cells by inactivating AKT

2021 ◽  
Vol 45 (4) ◽  
Author(s):  
Hao Zhou ◽  
Yichong Ning ◽  
Guirong Zeng ◽  
Chang Zhou ◽  
Xiaofeng Ding
Keyword(s):  
Cell Cycle ◽  
Acute Myeloid Leukemia ◽  
Cell Cycle Arrest ◽  
Myeloid Leukemia ◽  
Leukemia Cells ◽  
Cycle Arrest ◽  
Acute Myeloid Leukemia Cells ◽  
Acute Myeloid
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