scholarly journals Arsenic trioxide‑induced cell apoptosis and cell cycle arrest are potentiated by 1,25‑dihydroxyvitamin D3 in human leukemia K562 cells

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Ya-Li Zhang ◽  
Shu-Kai Qiao ◽  
Xiao-Nan Guo ◽  
Jin-Hai Ren ◽  
Jing-Nan Zhang
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Arsenic Trioxide ◽  
Cell Apoptosis ◽  
K562 Cells ◽  
Human Leukemia ◽  
Dihydroxyvitamin D3 ◽  
1,25 Dihydroxyvitamin D3 ◽  
Cycle Arrest ◽  
Human Leukemia K562 Cells

Induced Differentiation of U937 Cells by 1,25-dihydroxyvitamin D3 Involves Cell Cycle Arrest in G1 That Is Preceded by a Transient Proliferative Burst and an Increase in Cyclin Expression

Blood ◽  
1999 ◽  
Vol 93 (8) ◽  
pp. 2721-2729 ◽  
Author(s):  
Nynke Y. Rots ◽  
Antonio Iavarone ◽  
Virginia Bromleigh ◽  
Leonard P. Freedman
Keyword(s):  
Cell Cycle ◽  
Growth Inhibition ◽  
Cell Cycle Arrest ◽  
Cellular Proliferation ◽  
Leukemic Cells ◽  
Cdk Inhibitors ◽  
U937 Cells ◽  
Dihydroxyvitamin D3 ◽  
1,25 Dihydroxyvitamin D3 ◽  
Cycle Arrest

The hormonal form of vitamin D, 1,25-dihydroxyvitamin D3[1,25(OH)2D3], is a potent inhibitor of cellular proliferation as well as an inducer of differentiation of myeloid leukemic cells to macrophages. We have previously reported that a number of genes are upregulated by 1,25(OH)2D3 during myeloid differentiation, including the cyclin-dependent kinase (CDK) inhibitors p21, p27, 15, and p18, suggesting that cell cycle arrest and differentiation are tightly linked processes. We further explore here the relationship between growth inhibition and differentiation. We report that, upon 1,25(OH)2D3 treatment, U937 cells exhibited an early proliferative burst followed by growth inhibition and subsequent differentiation. Although CDK levels remain constant throughout, this transient increase in proliferation was accompanied by increases in cyclin A, D1, and E protein levels. p21 and p27 levels were also elevated during both the proliferative burst and subsequent inhibition of cell growth. Ectopic overexpression of p21 and/or p27 in U937 cells, in the absence of hormone, resulted in an induction of the expression of monocyte/macrophage-specific markers, whereas overexpression of p15 and p18 had no effect, suggesting that a subset of CDK inhibitors are important for both growth arrest and differentiation and that an early increase in proliferation is somehow a prerequisite for subsequent differentiation. However, no such biphasic behavior was detected in cells that are growth inhibited by 1,25(OH)2D3but do not differentiate, such as MCF-7 cells. Taken together, these results indicate that both growth stimulation and subsequent inhibition precede differentiation and involve induction of both cyclins and p21 and p27, whereas cell cycle arrest of differentiated cells can be achieved simply by elevations in CDK inhibitors.

scholarly journals Myc Inhibits p27-Induced Erythroid Differentiation of Leukemia Cells by Repressing Erythroid Master Genes without Reversing p27-Mediated Cell Cycle Arrest

2008 ◽  
Vol 28 (24) ◽  
pp. 7286-7295 ◽  
Author(s):  
Juan C. Acosta ◽  
Nuria Ferrándiz ◽  
Gabriel Bretones ◽  
Verónica Torrano ◽  
Rosa Blanco ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
K562 Cells ◽  
Erythroid Differentiation ◽  
Erythroid Cell ◽  
Specific Gene ◽  
Human Leukemia ◽  
Cycle Arrest ◽  
Conditional Expression ◽  
Inhibition Of Differentiation

ABSTRACT Inhibition of differentiation has been proposed as an important mechanism for Myc-induced tumorigenesis, but the mechanisms involved are unclear. We have established a genetically defined differentiation model in human leukemia K562 cells by conditional expression of the cyclin-dependent kinase (Cdk) inhibitor p27 (inducible by Zn2+) and Myc (activatable by 4-hydroxy-tamoxifen). Induction of p27 resulted in erythroid differentiation, accompanied by Cdk inhibition and G1 arrest. Interestingly, activation of Myc inhibited p27-mediated erythroid differentiation without affecting p27-mediated proliferation arrest. Microarray-based gene expression indicated that, in the presence of p27, Myc blocked the upregulation of several erythroid-cell-specific genes, including NFE2, JUNB, and GATA1 (transcription factors with a pivotal role in erythropoiesis). Moreover, Myc also blocked the upregulation of Mad1, a transcriptional antagonist of Myc that is able to induce erythroid differentiation. Cotransfection experiments demonstrated that Myc-mediated inhibition of differentiation is partly dependent on the repression of Mad1 and GATA1. In conclusion, this model demonstrates that Myc-mediated inhibition of differentiation depends on the regulation of a specific gene program, whereas it is independent of p27-mediated cell cycle arrest. Our results support the hypothesis that differentiation inhibition is an important Myc tumorigenic mechanism that is independent of cell proliferation.

Induced Differentiation of U937 Cells by 1,25-dihydroxyvitamin D3 Involves Cell Cycle Arrest in G1 That Is Preceded by a Transient Proliferative Burst and an Increase in Cyclin Expression

Blood ◽  
1999 ◽  
Vol 93 (8) ◽  
pp. 2721-2729 ◽  
Author(s):  
Nynke Y. Rots ◽  
Antonio Iavarone ◽  
Virginia Bromleigh ◽  
Leonard P. Freedman
Keyword(s):  
Cell Cycle ◽  
Growth Inhibition ◽  
Cell Cycle Arrest ◽  
Cellular Proliferation ◽  
Leukemic Cells ◽  
Cdk Inhibitors ◽  
U937 Cells ◽  
Dihydroxyvitamin D3 ◽  
1,25 Dihydroxyvitamin D3 ◽  
Cycle Arrest

Abstract The hormonal form of vitamin D, 1,25-dihydroxyvitamin D3[1,25(OH)2D3], is a potent inhibitor of cellular proliferation as well as an inducer of differentiation of myeloid leukemic cells to macrophages. We have previously reported that a number of genes are upregulated by 1,25(OH)2D3 during myeloid differentiation, including the cyclin-dependent kinase (CDK) inhibitors p21, p27, 15, and p18, suggesting that cell cycle arrest and differentiation are tightly linked processes. We further explore here the relationship between growth inhibition and differentiation. We report that, upon 1,25(OH)2D3 treatment, U937 cells exhibited an early proliferative burst followed by growth inhibition and subsequent differentiation. Although CDK levels remain constant throughout, this transient increase in proliferation was accompanied by increases in cyclin A, D1, and E protein levels. p21 and p27 levels were also elevated during both the proliferative burst and subsequent inhibition of cell growth. Ectopic overexpression of p21 and/or p27 in U937 cells, in the absence of hormone, resulted in an induction of the expression of monocyte/macrophage-specific markers, whereas overexpression of p15 and p18 had no effect, suggesting that a subset of CDK inhibitors are important for both growth arrest and differentiation and that an early increase in proliferation is somehow a prerequisite for subsequent differentiation. However, no such biphasic behavior was detected in cells that are growth inhibited by 1,25(OH)2D3but do not differentiate, such as MCF-7 cells. Taken together, these results indicate that both growth stimulation and subsequent inhibition precede differentiation and involve induction of both cyclins and p21 and p27, whereas cell cycle arrest of differentiated cells can be achieved simply by elevations in CDK inhibitors.

scholarly journals Harmine Hydrochloride Induced G2/M Phase Cell Cycle Arrest, Autophagy and Apoptosis in Human Leukemia K562 Cells through Modulation of the MAPK Pathway

2021 ◽  
Author(s):  
Zhilong Liu ◽  
Peng Zhang ◽  
Na Zhao ◽  
Lin-lin Lv ◽  
Ziyu Li ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Caspase 3 ◽  
K562 Cells ◽  
Leukemia Cells ◽  
Phase Cell ◽  
Human Leukemia ◽  
Cycle Arrest ◽  
Human Leukemia Cells ◽  
M Phase ◽  
Human Leukemia K562 Cells

Abstract Background Previous studies have indicated that harmine hydrochloride (HAR-HC) has anti-tumor characteristics. However, its potential impact on human leukemia cells is unknown. In this study, we explored the potential mechanism of HAR-HC effects on human leukemia cells in vitro. Methods MTT assay was used to detect cell viability; A flow cytometer was used to analyze the cell cycle; Anexinn V-FITC/PI was used to detect cell apoptosis; Western blotting assay was used to analyze the expression of related proteins. Results The result of flow cytometry suggested G2/M phage arrest in K562 cells induced by HAR-HC. The expression levels of Cyclin E2, Cyclin D1, Bcl-2, Bcl-xL, Mcl-1, pro-caspase-3, and PARP decreased and the expression levels of Cyclin A2, Cyclin B1, p21, Myt-1, p-cdc2 (Tyr15), cleaved -caspase-3 and cleaved-PARP increased. Moreover, the expression of p-JNK and p-ERK1/2 increased and autophagy was induced in the HAR-HC treatment group. Additionally, HAR-HC facilitated autophagy by activating the ERK1/2 pathway. Conclusion HAR-HC induced G2/M phase cell cycle arrest, autophagy and apoptosis by activating the JNK, and ERK1/2 pathways in the human leukemia K562 cells.

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