Ethyl Acetate Fraction of Papua’s Ant Nest Plant (Myrmecodia Pendens) Induces Cell Cycle Arrest and Apoptosis of an Oral Malignant Burkitt Lymphoma Cell through Down Regulation of Cyclin E–CDK2 Complex

2020 ◽  
Vol 11 (2) ◽  
pp. 1034
Author(s):  
Ana Medawati ◽  
Anon Supriatno ◽  
Sofia Mubarika ◽  
Sitarina Widyarini
Keyword(s):  
Cell Cycle ◽  
Ethyl Acetate ◽  
Cell Cycle Arrest ◽  
Burkitt Lymphoma ◽  
Cyclin E ◽  
Ethyl Acetate Fraction ◽  
Cycle Arrest ◽  
Burkitt Lymphoma Cell ◽  
Cdk2 Complex ◽  
Ant Nest

Ethyl acetate fraction of Garcina epunctata induces apoptosis in human promyelocytic cells (HL-60) through the ROS generation and G0/G1 cell cycle arrest: A bioassay-guided approach

2013 ◽  
Vol 36 (3) ◽  
pp. 865-874 ◽  
Author(s):  
Pieme Constant Anatole ◽  
Santoh Kumar Guru ◽  
Ngamegni Bathelemy ◽  
Ngogang Jeanne ◽  
Shashi Bhushan ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Ethyl Acetate ◽  
Cell Cycle Arrest ◽  
Ethyl Acetate Fraction ◽  
Ros Generation ◽  
Cycle Arrest ◽  
G1 Cell Cycle Arrest

scholarly journals Antiproliferative and proapoptotic effects of Inula viscosa extract on Burkitt lymphoma cell line

Tumor Biology ◽  
2020 ◽  
Vol 42 (2) ◽  
pp. 101042831990106 ◽  
Author(s):  
Patrizia Virdis ◽  
Rossana Migheli ◽  
Grazia Galleri ◽  
Silvia Fancello ◽  
Maria Piera L Cadoni ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cell Line ◽  
Burkitt Lymphoma ◽  
Cell Apoptosis ◽  
Molecular Mechanisms ◽  
Lymphoma Cell Line ◽  
Cycle Arrest ◽  
Burkitt Lymphoma Cell ◽  
Burkitt Lymphoma Cell Line

Burkitt lymphoma is a very aggressive B-cell non-Hodgkin lymphoma. Although remarkable progress has been made in the therapeutic scenario for patients with Burkitt lymphoma, search and development of new effective anticancer agents to improve patient outcome and minimize toxicity has become an urgent issue. In this study, the antitumoral activity of Inula viscosa, a traditional herb obtained from plants collected on the Asinara Island, Italy, was evaluated in order to explore potential antineoplastic effects of its metabolites on Burkitt lymphoma. Raji human cell line was treated with increasing Inula viscosa extract concentration for cytotoxicity screening and subsequent establishment of cell cycle arrest and apoptosis. Moreover, gene expression profiles were performed to identify molecular mechanisms involved in the anticancer activities of this medical plant. The Inula viscosa extract exhibited powerful antiproliferative and cytotoxic activities on Raji cell line, showing a dose- and time-dependent decrease in cell viability, obtained by cell cycle arrest in the G2/M phase and an increase in cell apoptosis. The treatment with Inula viscosa caused downregulation of genes involved in cell cycle and proliferation (c-MYC, CCND1) and inhibition of cell apoptosis (BCL2, BCL2L1, BCL11A). The Inula viscosa extract causes strong anticancer effects on Burkitt lymphoma cell line. The molecular mechanisms underlying such antineoplastic activity are based on targeting and downregulation of genes involved in cell cycle and apoptosis. Our data suggest that Inula viscosa natural metabolites should be further exploited as potential antineoplastic agents against Burkitt lymphoma.

Induction of apoptosis and cell cycle arrest by ethyl acetate fraction of Phoenix dactylifera L. (Ajwa dates) in prostate cancer cells

2018 ◽  
Vol 218 ◽  
pp. 35-44 ◽  
Author(s):  
Muqtadir Baig Mirza ◽  
Ayman I. Elkady ◽  
Atef M. Al-Attar ◽  
Fareeduddin Quadri Syed ◽  
Furkhan Ahmed Mohammed ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Cycle ◽  
Ethyl Acetate ◽  
Cancer Cells ◽  
Ethyl Acetate Fraction ◽  
Phoenix Dactylifera ◽  
Prostate Cancer Cells ◽  
Cycle Arrest ◽  
Phoenix Dactylifera L ◽  
Induction Of Apoptosis

scholarly journals Induction of Apoptosis, Autophagy and Ferroptosis by Thymus vulgaris and Arctium lappa Extract in Leukemia and Multiple Myeloma Cell Lines

Molecules ◽  
2020 ◽  
Vol 25 (21) ◽  
pp. 5016
Author(s):  
Aveen N. Adham ◽  
Mohamed Elamir F. Hegazy ◽  
Alaadin M. Naqishbandi ◽  
Thomas Efferth
Keyword(s):  
Cell Cycle ◽  
Multiple Myeloma ◽  
Cell Death ◽  
Ethyl Acetate ◽  
Cell Cycle Arrest ◽  
Cell Lines ◽  
Thymus Vulgaris ◽  
Arctium Lappa ◽  
Cycle Arrest ◽  
Induction Of Apoptosis

Thymus vulgaris and Arctium lappa have been used as a folk remedy in the Iraqi Kurdistan region to deal with different health problems. The aim of the current study is to investigate the cytotoxicity of T. vulgaris and A. lappa in leukemia and multiple myeloma (MM) cell lines and determine the mode of cell death triggered by the most potent cytotoxic fractions of both plants in MM. Resazurin assay was used to evaluate cytotoxic and ferroptosis activity, apoptosis, and modulation in the cell cycle phase were investigated via Annexin V-FITC/PI dual stain and cell-cycle arrest assays. Furthermore, we used western blotting assay for the determination of autophagy cell death. n-Hexane, chloroform, ethyl acetate, and butanol fractions of T. vulgaris and A. lappa exhibited cytotoxicity in CCRF-CEM and CEM/ADR 5000 cell lines at concentration range 0.001–100 μg/mL with potential activity revealed by chloroform and ethyl acetate fractions. NCI-H929 displayed pronounced sensitivity towards T. vulgaris (TCF) and A. lappa (ACF) chloroform fractions with IC50 values of 6.49 ± 1.48 and 21.9 ± 0.69 μg/mL, respectively. TCF induced apoptosis in NCI-H929 cells with a higher ratio (71%), compared to ACF (50%) at 4 × IC50. ACF demonstrated more potent autophagy activity than TCF. TCF and ACF induced cell cycle arrest and ferroptosis. Apigenin and nobiletin were identified in TCF, while nobiletin, ursolic acid, and lupeol were the main compounds identified in ACF. T. vulgaris and A. lappa could be considered as potential herbal drug candidates, which arrest cancer cell proliferation by induction of apoptosis, autophagic, and ferroptosis.

scholarly journals Differential Roles for Cyclin-Dependent Kinase Inhibitors p21 and p16 in the Mechanisms of Senescence and Differentiation in Human Fibroblasts

1999 ◽  
Vol 19 (3) ◽  
pp. 2109-2117 ◽  
Author(s):  
Gretchen H. Stein ◽  
Linda F. Drullinger ◽  
Alexandre Soulard ◽  
Vjekoslav Dulić
Keyword(s):  
Cell Cycle ◽  
Cyclin D1 ◽  
Cell Cycle Arrest ◽  
Early Stage ◽  
Cyclin E ◽  
Human Fibroblasts ◽  
Senescent Cell ◽  
Nuclear Antigen ◽  
Cyclin Dependent Kinase ◽  
Cycle Arrest

ABSTRACT The irreversible G1 arrest in senescent human diploid fibroblasts is probably caused by inactivation of the G1cyclin–cyclin-dependent kinase (Cdk) complexes responsible for phosphorylation of the retinoblastoma protein (pRb). We show that the Cdk inhibitor p21Sdi1,Cip1,Waf1, which accumulates progressively in aging cells, binds to and inactivates all cyclin E-Cdk2 complexes in senescent cells, whereas in young cells only p21-free Cdk2 complexes are active. Furthermore, the senescent-cell-cycle arrest occurs prior to the accumulation of the Cdk4-Cdk6 inhibitor p16Ink4a, suggesting that p21 may be sufficient for this event. Accordingly, cyclin D1-associated phosphorylation of pRb at Ser-780 is lacking even in newly senescent fibroblasts that have a low amount of p16. Instead, the cyclin D1-Cdk4 and cyclin D1-Cdk6 complexes in these cells are associated with an increased amount of p21, suggesting that p21 may be responsible for inactivation of both cyclin E- and cyclin D1-associated kinase activity at the early stage of senescence. Moreover, even in the late stage of senescence when p16 is high, cyclin D1-Cdk4 complexes are persistent, albeit reduced by ≤50% compared to young cells. We also provide new evidence that p21 may play a role in inactivation of the DNA replication factor proliferating cell nuclear antigen during early senescence. Finally, because p16 accumulates in parallel with the increases in senescence-associated β-Gal activity and cell volume that characterize the senescent phenotype, we suggest that p16 upregulation may be part of a differentiation program that is turned on in senescent cells. Since p21 decreases after senescence is achieved, this upregulation of p16 may be essential for maintenance of the senescent-cell-cycle arrest.

scholarly journals RIOK2 Inhibitor NSC139021 Exerts Anti-Tumor Effects on Glioblastoma via Inducing Skp2-Mediated Cell Cycle Arrest and Apoptosis

Biomedicines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 1244
Author(s):  
Min Yu ◽  
Xiaoyan Hu ◽  
Jingyu Yan ◽  
Ying Wang ◽  
Fei Lu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Signaling Pathway ◽  
Cyclin E ◽  
Intraperitoneal Administration ◽  
Glioblastoma Cells ◽  
P53 Signaling ◽  
Cycle Arrest ◽  
P53 Signaling Pathway

Up to now, the chemotherapy approaches for glioblastoma were limited. 1-[2-Thiazolylazo]-2-naphthol (named as NSC139021) was shown to significantly inhibit the proliferation of prostate cancer cells by targeting the atypical protein kinase RIOK2. It is documented that RIOK2 overexpressed in glioblastoma. However, whether NSC139021 can inhibit the growth of glioblastoma cells and be a potential drug for glioblastoma treatment need to be clarified. In this study, we investigated the effects of NSC139021 on human U118MG, LN-18, and mouse GL261 glioblastoma cells and the mouse models of glioblastoma. We verified that NSC139021 effectively inhibited glioblastoma cells proliferation, but it is independent of RIOK2. Our data showed that NSC139021 induced cell cycle arrest at G0/G1 phase via the Skp2-p27/p21-Cyclin E/CDK2-pRb signaling pathway in G1/S checkpoint regulation. In addition, NSC139021 also increased the apoptosis of glioblastoma cells by activating the p53 signaling pathway and increasing the levels of Bax and cleaved caspase 3. Furthermore, intraperitoneal administration of 150 mg/kg NSC139021 significantly suppressed the growth of human and mouse glioblastoma in vivo. Our study suggests that NSC139021 may be a potential chemotherapy drug for the treatment of glioblastoma by targeting the Skp2-p27/p21-Cyclin E/CDK2-pRb signaling pathway.

scholarly journals MDM4 is an essential disease driver targeted by 1q gain in Burkitt lymphoma

2018 ◽  
Author(s):  
Jennifer Hüllein ◽  
Mikołaj Słabicki ◽  
Maciej Rosolowski ◽  
Alexander Jethwa ◽  
Stefan Habringer ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Tumor Suppressor ◽  
Cell Cycle Arrest ◽  
Cell Lines ◽  
Burkitt Lymphoma ◽  
Mutant Cell ◽  
Negative Regulator ◽  
Dependent Manner ◽  
Cycle Arrest ◽  
1Q Gain

AbstractOncogenic MYC activation promotes cellular proliferation in Burkitt lymphoma (BL), but also induces cell cycle arrest and apoptosis mediated by TP53, a tumor suppressor gene that is mutated in 40% of BL cases. To identify therapeutic targets in BL, we investigated molecular dependencies in BL cell lines using RNAi-based, loss-of-function screening. By integrating genotypic and RNAi data, we identified a number of genotype-specific dependencies including the dependence of TCF3/ID3 mutant cell lines on TCF3 and of MYD88 mutant cell lines on TLR signaling. TP53 wild-type (TP53wt) BL were dependent on MDM4, a negative regulator of TP53. In BL cell lines, MDM4 knockdown induced cell cycle arrest and decreased tumor growth in a xenograft model in a p53-dependent manner, while small molecule inhibition of the MDM4-p53 interaction restored p53 activity resulting in cell cycle arrest. Consistent with the pathogenic effect of MDM4 upregulation in BL, we found that TP53wt BL samples were enriched for gain of chromosome 1q which includes the MDM4 locus. 1q gain was also enriched across non-BL cancer cell lines (n=789) without TP53 mutation (23% in TP53wt and 12% in TP53mut, p<0.001). In a set of 216 cell lines representing 19 cancer entities from the Achilles project, MDM4 was the strongest genetic dependency in TP53wt cell lines (p<0.001).Our findings show that in TP53wt BL, MDM4-mediated inhibition of p53 is a mechanism to evade cell cycle arrest. The data highlight the critical role of p53 as a tumor suppressor in BL, and identifies MDM4 as a key functional target of 1q gain in a wide range of cancers, which is therapeutically targetable.

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