The Effect of Calcium Canal Blocker, Verapamil, on Cell Cycle and Apoptosis in Acute Myeloid Leukemia Cancer Cell Line (HL-60)

Abstract BackgroundCluster of Differentiation 80 and CD 86 can also be called B7-1 and B7-2 respectively. They are proteins fundamentally expressed on antigen-presenting cells (APCs), including induced dendritic cells (IDCs), langerhans cells, germinal center dendritic cells (GCDCs), activated monocytes, macrophages and B-cells. They are considered to be a possible therapeutic target and biomarker of great significance. However, there are still inconsistent pieces of information and their clinical importance is yet to be established. MethodsHere we investigated CD 80 and 86 as biomarkers by utilizing several large genomic data collections. (The Cancer Genome Atlas, Cancer Cell Line Encyclopedia, Quantitative proteomics Cancer cell line Encyclopedia Genotype-Tissue Expression,) and analyzed CD 80 and CD 86 expression in thousands of normal and cancer samples and cell lines along with their clinical survival analysis.ResultsThis study presented that CD 86 was expressed more in post-treatment blood cancer in the blood and post-treatment blood cancer in the bone marrow while it was expressed least in normal tissues and cell lines. The Hodgkin lymphoma cell line L428 cell lysate illustrated that there was a high relative protein expression of 6.6 for the CD 86 gene. it indicated that cancer in the esophagus had the highest copy number value and indicated a medium level amplification of the CD 86 gene and prostate cancer had a hemizygous deletion of the CD 86 gene with the least copy number value. Furthermore, on the non-Hodgkin lymphoma cell line REC1, illustrated the highest relative protein expression of the CD 86 gene among the other types of cancer cell line, its protein expression value was 8.19. Also, for cancer type leukemia, the subtype acute myeloid leukemia showed a significant relative protein expression. The acute myeloid leukemia cell line EOL1 indicated that there was a high relative protein expression of 6.5. However, the protein expression for CD 80 is yet to be elucidated.ConclusionsTaken together, CD 80 ad 86 may be potential biomarkers of great clinical significance. The Kaplan Meier plots unveiled that CD 86 and CD 80 were significantly associated with overall survival analysis in the Large B-cell lymphoma, and the different tumor types.

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Essential Role for Phospholipase C Gamma 1 (PLC-γ1) in the Survival of t(8;21) Acute Myeloid Leukemia

Blood ◽

10.1182/blood.v128.22.1699.1699 ◽

2016 ◽

Vol 128 (22) ◽

pp. 1699-1699 ◽

Cited By ~ 1

Author(s):

Hasan Mahmud ◽

Frank JG Scherpen ◽

Tiny Meeuwsen-de Boer ◽

Harm-Jan Lourens ◽

Eveline S. de Bont

Keyword(s):

Cell Cycle ◽

Acute Myeloid Leukemia ◽

Phospholipase C ◽

Cell Line ◽

Myeloid Leukemia ◽

Genetic Alterations ◽

Therapeutic Strategies ◽

Mrna Levels ◽

Phospholipase C Gamma ◽

Acute Myeloid

Abstract The t(8;21) (q22;q22) chromosomal translocation is one of the most frequent genetic alterations in acute myeloid leukemia (AML) and it remains a significant clinical problem especially for children which indicates the need for improved therapeutic strategies. Recently, we showed that peptide derived phospholipase C gamma 1 (PLC-γ1) was highly phosphorylated in pediatric t(8;21) AML. In this study, we determined PLC-γ1 phosphorylation and mRNA levels showing that PLC-γ1 expression was significantly higher in t(8;21) AML compared to other AML karyotypes and normal bone marrow (NBM) (peptide phosphorylation: p<0.01 compared to NBM, mRNA: p<0.001, compared to other AML karyotypes). This was confirmed by PLC-γ1 protein phosphorylation using primary AML samples and AML cell lines. PLC-γ1 is known to play a role in cancer progression, however, the impact of PLC-γ1 in AML is currently unknown. Therefore, we aimed to study the functional role of PLC-γ1 by investigating the cellular growth, survival and its underlying mechanism in a t(8;21) AML cell line (Kasumi-1) . ShRNA-mediated knockdown of PLC-γ1 in kasumi-1 cells significantly blocked leukemic cell growth at day 8 after transduction (p<0.05). The percentage of apoptosis in PLC-γ1 suppressed kasumi-1 cells at day 4 after transduction was two-fold higher compared to the scrambled control (p<0.01). The inhibition of cell proliferation and the induction of apoptosis upon PLC-γ1 suppression could be explained by cell cycle arrest and by increased activation of apoptotic related and cell cycle regulatory protein expressions (BAX, BCL2, p53 and Chk2). As the multidrug resistance is one of the major cause of relapse and poor prognosis in t(8;21) AML, therefore, we demonstrated, if PLC-γ1 suppression increased the sensitivity of kasumi-1 leukemia cells to cytotoxic chemotherapeutic agents (methotrexate, amsacrine and etoposide). PLC-γ1 knockdown cells at day 4 after transduction were shown to significantly reduced cell viability to the genotoxic agents, methotrexate (p<0.05, p<0.001), amsacrine (p<0.01, p<0.001) and etoposide (p<0.05, p<0.01 and p<0.001) in kasumi-1 in a dose-dependent manner. These results provide a strong rationale for the development of PLC-γ1-based therapeutic strategies for the enhancement of efficacy in t(8;21) AML treatment. Additionally, PLC-γ1 suppressed kasumi-1 cells showed significantly less proliferation upon hypoxic stress. Taken together, these results strongly support an important role for PLC-γ1 in the survival of t(8;21) AML mimicking kasumi-1 cell line and identify PLC-γ1 as a potential target for t(8;21) AML treatment. Disclosures No relevant conflicts of interest to declare.

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Alloimperatorin and its epoxide derivative exhibit in vitro antitumor activity in HL-60 acute myeloid leukemia cancer cells via inducing apoptosis, cell cycle disruption and inhibition of cell migration

Bangladesh Journal of Pharmacology ◽

10.3329/bjp.v11i1.24575 ◽

2016 ◽

Vol 11 (1) ◽

pp. 194 ◽

Cited By ~ 1

Author(s):

Hong Li ◽

Xu Chao ◽

Chun-Ling He ◽

Xin-Mei Wang ◽

Man Liang ◽

...

Keyword(s):

Cell Cycle ◽

Acute Myeloid Leukemia ◽

Cell Migration ◽

Cancer Cell ◽

Myeloid Leukemia ◽

Cancer Metastasis ◽

Phase Cell ◽

Cancer Cell Migration ◽

Acute Myeloid

The aim of the present study was to synthesize epoxide derivative of alloimperatorin and evaluating its antitumor and apoptotic effects in acute myeloid leukemia HL-60 cells. The cytotoxic effects were demonstrated by MTT assay. Fluorescence microscopy along with flow cytometry were performed to evaluate the effect of alloimperatorin epoxide on apoptosis and cell cycle. In vitro wound healing assay was performed to study compound’s effect on cancer cell migration. The results indicated that alloimperatorin epoxide (IC50 = 32.1 µM) was much more effective in inhibiting HL-60 cancer cell growth as compared to alloimperatorin (IC50 = 128 µM). Further, alloimperatorin epoxide induced apoptosis related morphological alterations in HL-60 cells including blebbing of plasma membrane, DNA fragmentation and formation of apoptotic bodies. Alloimperatorin epoxide also led to G2/M phase cell cycle arrest and suppressed HL-60 cancer cell migration indicating that this compound may be a promising candidate for the treatment of cancer metastasis.

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Artesunate induces prostate cancer cell line PC-3 differentiation and cell cycle arrest

Journal of Chinese Integrative Medicine ◽

10.3736/jcim20080609 ◽

2008 ◽

Vol 6 (6) ◽

pp. 591-594 ◽

Cited By ~ 2

Author(s):

Xiao fei Huang

Keyword(s):

Prostate Cancer ◽

Cell Cycle ◽

Cell Cycle Arrest ◽

Cell Line ◽

Cancer Cell ◽

Prostate Cancer Cell ◽

Cancer Cell Line ◽

Prostate Cancer Cell Line ◽

Cycle Arrest

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Antitumor Effect of Pomolic Acid in Acute Myeloid Leukemia Cells Involves Cell Death, Decreased Cell Growth and Topoisomerases Inhibition

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520618666180412120128 ◽

2019 ◽

Vol 18 (10) ◽

pp. 1457-1468

Author(s):

Michelle X.G. Pereira ◽

Amanda S.O. Hammes ◽

Flavia C. Vasconcelos ◽

Aline R. Pozzo ◽

Thaís H. Pereira ◽

...

Keyword(s):

Cell Cycle ◽

Cell Death ◽

Acute Myeloid Leukemia ◽

Cell Lines ◽

Myeloid Leukemia ◽

Natural Compound ◽

Dna Topoisomerases ◽

Human Dna ◽

Pomolic Acid ◽

Acute Myeloid

Background: Acute myeloid leukemia (AML) represents the largest number of annual deaths from hematologic malignancy. In the United States, it was estimated that 21.380 individuals would be diagnosed with AML and 49.5% of patients would die in 2017. Therefore, the search for novel compounds capable of increasing the overall survival rate to the treatment of AML cells is urgent. Objectives: To investigate the cytotoxicity effect of the natural compound pomolic acid (PA) and to explore the mechanism of action of PA in AML cell lines with different phenotypes. Methods: Three different AML cell lines, HL60, U937 and Kasumi-1 cells with different mechanisms of resistance were used to analyze the effect of PA on the cell cycle progression, on DNA intercalation and on human DNA topoisomerases (hTopo I and IIα) in vitro studies. Theoretical experiments of the inhibition of hTopo I and IIα were done to explore the binding modes of PA. Results: PA reduced cell viability, induced cell death, increased sub-G0/G1 accumulation and activated caspases pathway in all cell lines, altered the cell cycle distribution and inhibited the catalytic activity of both human DNA topoisomerases. Conclusion: Finally, this study showed that PA has powerful antitumor activity against AML cells, suggesting that this natural compound might be a potent antineoplastic agent to improve the treatment scheme of this neoplasm.

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ATF3 coordinates serine and nucleotide metabolism to drive cell cycle progression in acute myeloid leukemia

Molecular Cell ◽

10.1016/j.molcel.2021.05.008 ◽

2021 ◽

Author(s):

Daniela Di Marcantonio ◽

Esteban Martinez ◽

Joice S. Kanefsky ◽

Jacklyn M. Huhn ◽

Rashid Gabbasov ◽

...

Keyword(s):

Cell Cycle ◽

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Cell Cycle Progression ◽

Nucleotide Metabolism ◽

Cycle Progression ◽

Acute Myeloid

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Monochloramine suppresses the proliferation of colorectal cancer cell line Caco-2 by both apoptosis and G2/M cell cycle arrest

Cell Biochemistry and Function ◽

10.1002/cbf.2992 ◽

2013 ◽

Vol 32 (2) ◽

pp. 188-193 ◽

Cited By ~ 1

Author(s):

Tetsuya Kohda ◽

Satoru Sakuma ◽

Muneyuki Abe ◽

Yohko Fujimoto

Keyword(s):

Colorectal Cancer ◽

Cell Cycle ◽

Cell Cycle Arrest ◽

Cell Line ◽

Cancer Cell ◽

Cancer Cell Line ◽

Colorectal Cancer Cell ◽

Colorectal Cancer Cell Line ◽

M Cell ◽

Cycle Arrest

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Chamaejasmine Arrests Cell Cycle, Induces Apoptosis and Inhibits Nuclear NF-κB Translocation in the Human Breast Cancer Cell Line MDA-MB-231

Molecules ◽

10.3390/molecules18010845 ◽

2013 ◽

Vol 18 (1) ◽

pp. 845-858 ◽

Cited By ~ 18

Author(s):

Tingting Zhang ◽

Hongyang Yu ◽

Guanglu Dong ◽

Li Cai ◽

Yuxian Bai

Keyword(s):

Breast Cancer ◽

Cell Cycle ◽

Cell Line ◽

Cancer Cell ◽

Breast Cancer Cell ◽

Breast Cancer Cell Line ◽

Human Breast Cancer ◽

Cancer Cell Line ◽

Human Breast Cancer Cell ◽

Human Breast

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

Chemotherapy ◽

10.1159/000491705 ◽

2018 ◽

Vol 63 (4) ◽

pp. 225-237 ◽

Cited By ~ 1

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.

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