669 P21WAF1 Represses Cell Cycle Genes in K562 Cells Acting as a Transcriptional Modulator

Cancer cells are altered with cell cycle genes or they are mutated, leading to a high rate of proliferation compared to normal cells. Alteration in these genes leads to mitosis dysregulation and becomes the basis of tumor progression and resistance to many drugs. The drugs which act on the cell cycle fail to arrest the process, making cancer cell non-responsive to apoptosis or cell death. Vinca alkaloids and taxanes fall in this category and are referred to as antimitotic agents. Microtubule proteins play an important role in mitosis during cell division as a target site for vinca alkaloids and taxanes. These proteins are dynamic in nature and are composed of α-β-tubulin heterodimers. β-tubulin specially βΙΙΙ isotype is generally altered in expression within cancerous cells. Initially, these drugs were very effective in the treatment of cancer but failed to show their desired action after initial chemotherapy. The present review highlights some of the important targets and their mechanism of resistance offered by cancer cells with new promising drugs from natural sources that can lead to the development of a new approach to chemotherapy.

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Overexpression of β-Arrestins inhibits proliferation and motility in triple negative breast cancer cells

Scientific Reports ◽

10.1038/s41598-021-80974-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Saber Yari Bostanabad ◽

Senem Noyan ◽

Bala Gur Dedeoglu ◽

Hakan Gurdal

Keyword(s):

Breast Cancer ◽

Cell Cycle ◽

Cancer Cells ◽

Cancer Cell ◽

Breast Cancer Cells ◽

Cell Function ◽

Expression Profiles ◽

Tissue Samples ◽

Expression Levels ◽

Cell Cycle Genes

Abstractβ-Arrestins (βArrs) are intracellular signal regulating proteins. Their expression level varies in some cancers and they have a significant impact on cancer cell function. In general, the significance of βArrs in cancer research comes from studies examining GPCR signalling. Given the diversity of different GPCR signals in cancer cell regulation, contradictory results are inevitable regarding the role of βArrs. Our approach examines the direct influence of βArrs on cellular function and gene expression profiles by changing their expression levels in breast cancer cells, MDA-MB-231 and MDA-MB-468. Reducing expression of βArr1 or βArr2 tended to increase cell proliferation and invasion whereas increasing their expression levels inhibited them. The overexpression of βArrs caused cell cycle S-phase arrest and differential expression of cell cycle genes, CDC45, BUB1, CCNB1, CCNB2, CDKN2C and reduced HER3, IGF-1R, and Snail. Regarding to the clinical relevance of our results, low expression levels of βArr1 were inversely correlated with CDC45, BUB1, CCNB1, and CCNB2 genes compared to normal tissue samples while positively correlated with poorer prognosis in breast tumours. These results indicate that βArr1 and βArr2 are significantly involved in cell cycle and anticancer signalling pathways through their influence on cell cycle genes and HER3, IGF-1R, and Snail in TNBC cells.

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Synthesis and anticancer evaluation of sulfur containing 9-anilinoacridines

Recent Patents on Anti-Cancer Drug Discovery ◽

10.2174/1574892816666210728122910 ◽

2021 ◽

Vol 16 ◽

Author(s):

Pranav Gupta ◽

Radhika V. Kumar ◽

Chul-Hoon Kwon ◽

Zhe-Sheng Chen

Keyword(s):

Cell Cycle ◽

Anticancer Activity ◽

Topoisomerase Ii ◽

Critical Role ◽

K562 Cells ◽

Dependent Manner ◽

Concentration Dependent Manner ◽

In Vivo Models ◽

Topo Ii ◽

Sulfur Containing

Background: DNA topoisomerases are a class of enzymes that play a critical role in fundamental biological processes of replication, transcription, recombination, repair and chromatin remodeling. Amsacrine (m-AMSA), the best-known compound of 9-anilinoacridines series was one of the first DNA-intercalating agents to be considered as a Topoisomerase II inhibitor. Objective: A series of sulfur containing 9-anilinoacridines related to amsacrine were synthesized and evaluated for their anticancer activity. Methods: Cell viability was assessed by the MTT assay. The topoisomerase II inhibitory assay was performed using the Human topoisomerase II Assay kit and flow cytometry was used to evaluate the effects on cell cycle of K562 cells. Molecular docking was performed using Schrödinger Maestro program. Results: Compound 36 was found to be the most cytotoxic of the sulfide series against SW620, K562, and MCF-7. The limited SAR suggested the importance of the methansulfonamidoacetamide side chain functionality, the lipophilicity and relative metabolic stability of 36 in contributing to the cytotoxicity. Topoisomerase II α inhibitory activity appeared to be involved in the cytotoxicity of 36 through inhibition of decatenation of kinetoplast DNA (kDNA) in a concentration dependent manner. Cell cycle analysis further showed the Topo II inhibition through accumulation of K562 cells in G2/M phase of cell cycle. Docking of 36 into the Topo II α-DNA complex suggested that it may be an allosteric inhibitor of Topo II α. Conclusion: Compound 36 exhibits anticancer activity by inhibiting topoisomerase II and it could further be evaluated in in vivo models.

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Role of Cell-Cycle Genes in the Regulation of Mammalian Meiosis

Germ Cell Development, Division, Disruption and Death ◽

10.1007/978-1-4612-2206-4_6 ◽

1998 ◽

pp. 49-60 ◽

Cited By ~ 2

Author(s):

Debra J. Wolgemuth ◽

Valerie Besset ◽

Dong Liu ◽

Qi Zhang ◽

Kunsoo Rhee

Keyword(s):

Cell Cycle ◽

Cell Cycle Genes

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Cell cycle genes and spermatogenesis in the sea star, Asterias vulgaris

Echinoderms through Time ◽

10.1201/9781003077831-89 ◽

2020 ◽

pp. 381-381

Author(s):

C.W. Walker

Keyword(s):

Cell Cycle ◽

Sea Star ◽

Cell Cycle Genes ◽

Asterias Vulgaris

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Correction: Wogonin induces cell cycle arrest and erythroid differentiation in imatinib-resistant K562 cells and primary CML cells

Oncotarget ◽

10.18632/oncotarget.27373 ◽

2020 ◽

Vol 11 (3) ◽

pp. 300-301

Author(s):

Hao Yang ◽

Hui Hui ◽

Qian Wang ◽

Hui Li ◽

Kai Zhao ◽

...

Keyword(s):

Cell Cycle ◽

Cell Cycle Arrest ◽

K562 Cells ◽

Erythroid Differentiation ◽

Cycle Arrest ◽

Imatinib Resistant

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Genome-Wide Identification and Analysis of Cell Cycle Genes in Birch

Forests ◽

10.3390/f13010120 ◽

2022 ◽

Vol 13 (1) ◽

pp. 120

Author(s):

Yijie Li ◽

Song Chen ◽

Yuhang Liu ◽

Haijiao Huang

Keyword(s):

Cell Cycle ◽

Growth And Development ◽

Betula Pendula ◽

Cell Cycle Gene ◽

Expression Data ◽

Rna Seq ◽

Specific Expression ◽

Cell Cycles ◽

Cell Cycle Genes ◽

Genome Wide

Research Highlights: This study identified the cell cycle genes in birch that likely play important roles during the plant’s growth and development. This analysis provides a basis for understanding the regulatory mechanism of various cell cycles in Betula pendula Roth. Background and Objectives: The cell cycle factors not only influence cell cycles progression together, but also regulate accretion, division, and differentiation of cells, and then regulate growth and development of the plant. In this study, we identified the putative cell cycle genes in the B. pendula genome, based on the annotated cell cycle genes in Arabidopsis thaliana (L.) Heynh. It can be used as a basis for further functional research. Materials and Methods: RNA-seq technology was used to determine the transcription abundance of all cell cycle genes in xylem, roots, leaves, and floral tissues. Results: We identified 59 cell cycle gene models in the genome of B. pendula, with 17 highly expression genes among them. These genes were BpCDKA.1, BpCDKB1.1, BpCDKB2.1, BpCKS1.2, BpCYCB1.1, BpCYCB1.2, BpCYCB2.1, BpCYCD3.1, BpCYCD3.5, BpDEL1, BpDpa2, BpE2Fa, BpE2Fb, BpKRP1, BpKRP2, BpRb1, and BpWEE1. Conclusions: By combining phylogenetic analysis and tissue-specific expression data, we identified 17 core cell cycle genes in the Betulapendula genome.

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Antiproliferative and Apoptosis-Inducing Activities of Benchalokawichian Remedy Against Doxorubicin-Sensitive and -Resistant Erythromyelogenous Leukemic Cells

Chiang Mai University Journal of Natural Sciences ◽

10.12982/cmujns.2021.056 ◽

2021 ◽

Vol 20 (3) ◽

Author(s):

Wipob Suttana ◽

Chatubhong Singharachai ◽

Rawiwan Charoensup ◽

Narawadee Rujanapun ◽

Chutima Suya

Keyword(s):

Cell Cycle ◽

Multidrug Resistance ◽

Cell Cycle Arrest ◽

Cancer Cells ◽

K562 Cells ◽

Leukemic Cells ◽

Drug Resistant ◽

Normal Cells ◽

Root Extracts ◽

Cycle Arrest

Chemotherapy can cause multidrug resistance in cancer cells and is cytotoxic to normal cells. Discovering natural bioactive compounds that are not cytotoxic to normal cells but inhibit proliferation and induce apoptosis in drug- sensitive and drug-resistant cancer cells could overcome these drawbacks of chemotherapy. This study investigated the antiproliferative effects of crude extracts of Benchalokawichian (BLW) remedy and its herbal components against drug-sensitive and drug-resistant cancer cells, cytotoxicity of the extracts toward normal cells, and their ability to induce apoptosis and cell cycle arrest in drug-sensitive and drug-resistant cancer cells. The extracts exhibited antiproliferative activity against doxorubicin-sensitive and doxorubicin-resistant erythromyelogenous leukemic cells (K562 and K562/adr). Tiliacora triandra root, BLW, and Harrisonia perforata root extracts displayed an IC50 of 77.00 ± 1.30, 79.33 ± 1.33, and 87.67 ± 0.67 µg/mL, respectively, against K562 cells. In contrast, Clerodendrum petasites, T. triandra, and H. perforata root extracts displayed the lowest IC50 against K562/adr cells (68.89 ± 0.75, 78.33 ± 0.69, and 86.78 ± 1.92 µg/mL, respectively). The resistance factor of the extracts was lower than that of doxorubicin, indicating that the extracts could overcome the multidrug resistance of cancer cells. Importantly, the extracts were negligibly cytotoxic to peripheral mononuclear cells, indicating minimal adverse effects in normal cells. In addition, these extracts induced apoptosis of K562 and K562/adr cells and caused cell cycle arrest at the G0/G1 phase in K562 cells. Keywords: Antiproliferative, Apoptosis, Benchalokawichian, Cell cycle, Multidrug resistance

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Induction of apoptosis by Kola nut extract as a recent and promising treatment strategy for Leukemia

Bionatura ◽

10.21931/rb/2021.06.02.10 ◽

2021 ◽

Vol 6 (2) ◽

pp. 1725-1732

Author(s):

Hamdah Alsaeedi ◽

Rowaid Qahwaji ◽

Talal Qadah

Keyword(s):

Cell Cycle ◽

Cell Line ◽

Leukemia Cell ◽

K562 Cells ◽

Myelogenous Leukemia ◽

Time Dependent ◽

Leukemia Cell Line ◽

Apoptotic Cells ◽

Dependent Manner ◽

Anti Cancer

Kola nut extracts have recently been reported to contain chemopreventive compounds providing several pharmacological benefits. This study investigated Kola nut extracts' anti-cancer activity on human immortalized myelogenous leukemia cell line K562 through apoptosis and cell cycle arrest. Fresh Kola nuts were prepared as powder and dissolved in DMSO. Different concentrations (50, 100, 150, 200, and 250 μg/ml) of working solutions were prepared. The K562 cells were treated with the different concentrations of Kola nut extract or vehicle control (10% DMSO) followed by incubation at 37°C for 24, 48, and 72 hours, respectively. Treatment activity was investigated in K562 cells; by Resazurin, and FITC/Propidium Iodide and 7-AAD stained cells to evaluate apoptotic cells and the cell cycle's progression. Inhibition of leukemia cell proliferation was observed. The extract effectively induced cell death, early and late apoptosis by approximately 30% after 24 and 48 hours incubation, and an increase in the rate of dead cells by 50% was observed after 72 hours of incubation. Also, cell growth reduction was seen at high dose concentrations (150 and 200 µg/ml), as evident by cell count once treated with Kola nut extract. The total number of apoptotic cells increased from 5.8% of the control group to 27.4% at 250 µg/ml concentration. Moreover, Kola nut extracts' effects on K562 cells increased gradually in a dose and time-dependent manner. It was observed that Kola nut extracts could arrest the cell cycle in the G2/M phase as an increase in the number of cells by 29.8% and 14.6 % were observed from 9.8% and 5.2% after 24 and 48 hours of incubation, respectively. This increase was detected in a dose and time-dependent manner. Kola nut extracts can be used as a novel anti-cancer agent in Leukemia treatment as it has shown significant therapeutic potential and therefore provides new insights in understanding the mechanisms of its action. Keywords: Kola nut extracts, Leukemia, K562 cell line, Apoptosis, Cancer.

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