W436, a novel SMART derivative, exhibits anti‐hepatocarcinoma activity by inducing apoptosis and G2/M cell cycle arrest in vitro and in vivo and induces protective autophagy

Background: Cholangiocarcinoma (CCA) is an extremely intractable malignancy since most patients are already in an advanced stage when firstly discovered. CCA needs more effective treatment, especially for advanced cases. Our study aimed to evaluate the effect of romidepsin on CCA cells in vitro and in vivo and explore the underlying mechanisms. Methods: The antitumor effect was determined by cell viability, cell cycle and apoptosis assays. A CCK-8 assay was performed to measure the cytotoxicity of romidepsin on CCA cells, and flow cytometry was used to evaluate the effects of romidepsin on the cell cycle and apoptosis. Moreover, the in vivo effects of romidepsin were measured in a CCA xenograft model. Results: Romidepsin could reduce the viability of CCA cells and induce G2/M cell cycle arrest and apoptosis, indicating that romidepsin has a significant antitumor effect on CCA cells in vitro. Mechanistically, the antitumor effect of romidepsin on the CCA cell lines was mediated by the induction of G2/M cell cycle arrest and promotion of cell apoptosis. The G2/M phase arrest of the CCA cells was associated with the downregulation of cyclinB and upregulation of the p-cdc2 protein, resulting in cell cycle arrest. The apoptosis of the CCA cells induced by romidepsin was attributed to the activation of caspase-3. Furthermore, romidepsin significantly inhibited the growth of the tumor volume of the CCLP-1 xenograft, indicating that romidepsin significantly inhibited the proliferation of CCA cells in vivo. Conclusions: Romidepsin suppressed the proliferation of CCA cells by inducing cell cycle arrest through cdc2/cyclinB and cell apoptosis by targeting caspase-3/PARP both in vitro and in vivo, indicating that romidepsin is a potential therapeutic agent for CCA.

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Digitoxin inhibits HeLa cell growth through the induction of G2/M cell cycle arrest and apoptosis in vitro and in vivo

International Journal of Oncology ◽

10.3892/ijo.2020.5070 ◽

2020 ◽

Vol 57 (2) ◽

pp. 562-573

Author(s):

Hua Gan ◽

Ming Qi ◽

Chakpiu Chan ◽

Pan Leung ◽

Geni Ye ◽

...

Keyword(s):

Cell Cycle ◽

Cell Growth ◽

Hela Cell ◽

Cell Cycle Arrest ◽

M Cell ◽

Cycle Arrest

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Piperlongumine induces gastric cancer cell apoptosis and G2/M cell cycle arrest both in vitro and in vivo

Tumor Biology ◽

10.1007/s13277-016-4792-9 ◽

2016 ◽

Vol 37 (8) ◽

pp. 10793-10804 ◽

Cited By ~ 26

Author(s):

Chaoqin Duan ◽

Bin Zhang ◽

Chao Deng ◽

Yu Cao ◽

Fan Zhou ◽

...

Keyword(s):

Gastric Cancer ◽

Cell Cycle ◽

Cell Cycle Arrest ◽

Cancer Cell ◽

Cell Apoptosis ◽

Gastric Cancer Cell ◽

M Cell ◽

Cycle Arrest

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Curcumin induces G2/M cell cycle arrest and apoptosis of head and neck squamous cell carcinoma in vitro and in vivo through ATM/Chk2/p53-dependent pathway

Oncotarget ◽

10.18632/oncotarget.17096 ◽

2017 ◽

Vol 8 (31) ◽

pp. 50747-50760 ◽

Cited By ~ 21

Author(s):

An Hu ◽

Jing-Juan Huang ◽

Jing-Fei Zhang ◽

Wei-Jun Dai ◽

Rui-Lin Li ◽

...

Keyword(s):

Cell Cycle ◽

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Head And Neck ◽

Cell Cycle Arrest ◽

M Cell ◽

Cycle Arrest ◽

Dependent Pathway

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Dual effect of 2-methoxyestradiol on cell cycle events in human osteosarcoma 143B cells.

Acta Biochimica Polonica ◽

10.18388/abp.2002_3821 ◽

2002 ◽

Vol 49 (1) ◽

pp. 59-65 ◽

Cited By ~ 16

Author(s):

Justyna Gołebiewska ◽

Piotr Rozwadowski ◽

Jan Henryk Spodnik ◽

Narcyz Knap ◽

Takashi Wakabayashi ◽

...

Keyword(s):

Cell Cycle ◽

Cell Cycle Arrest ◽

Growth Inhibitor ◽

Cytotoxic Action ◽

M Cell ◽

Human Osteosarcoma ◽

Cycle Arrest ◽

M Phase ◽

The Stability

We have demonstrated for the first time that the steroid metabolite, 2-methoxyestradiol (2-ME) is a powerful growth inhibitor of human osteosarcoma 143 B cell line by pleiotropic mechanisms involving cell cycle arrest at two different points and apoptosis. The ability of 2-ME to inhibit cell cycle at the respective points has been found concentration dependent. 1 microM 2-ME inhibited cell cycle at G1 phase while 10 microM 2-ME caused G2/M cell cycle arrest. As a natural estrogen metabolite 2-ME is expected to perturb the stability of microtubules (MT) in vivo analogously to Taxol--the MT binding anticancer agent. Contrary to 2-ME, Taxol induced accumulation of osteosarcoma cells in G2/M phase of cell cycle only. The presented data strongly suggest two different mechanisms of cytotoxic action of 2-ME at the level of a single cell.

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Menadione reduces CDC25B expression and promotes tumor shrinkage in gastric cancer

Therapeutic Advances in Gastroenterology ◽

10.1177/1756284819895435 ◽

2020 ◽

Vol 13 ◽

pp. 175628481989543

Author(s):

Amanda Braga Bona ◽

Danielle Queiroz Calcagno ◽

Helem Ferreira Ribeiro ◽

José Augusto Pereira Carneiro Muniz ◽

Giovanny Rebouças Pinto ◽

...

Keyword(s):

Gastric Cancer ◽

Cell Cycle ◽

Cell Cycle Arrest ◽

Cell Lines ◽

Specific Inhibitor ◽

Gastric Carcinogenesis ◽

In Vivo Experiments ◽

Cycle Arrest

Background: Gastric cancer is one of the most incident types of cancer worldwide and presents high mortality rates and poor prognosis. MYC oncogene overexpression is a key event in gastric carcinogenesis and it is known that its protein positively regulates CDC25B expression which, in turn, plays an essential role in the cell division cycle progression. Menadione is a synthetic form of vitamin K that acts as a specific inhibitor of the CDC25 family of phosphatases. Methods: To better understand the menadione mechanism of action in gastric cancer, we evaluated its molecular and cellular effects in cell lines and in Sapajus apella, nonhuman primates from the new world which had gastric carcinogenesis induced by N-Methyl-N-nitrosourea. We tested CDC25B expression by western blot and RT-qPCR. In-vitro assays include proliferation, migration, invasion and flow cytometry to analyze cell cycle arrest. In in-vivo experiments, in addition to the expression analyses, we followed the preneoplastic lesions and the tumor progression by ultrasonography, endoscopy, biopsies, histopathology and immunohistochemistry. Results: Our tests demonstrated menadione reducing CDC25B expression in vivo and in vitro. It was able to reduce migration, invasion and proliferation rates, and induce cell cycle arrest in gastric cancer cell lines. Moreover, our in-vivo experiments demonstrated menadione inhibiting tumor development and progression. Conclusions: We suggest this compound may be an important ally of chemotherapeutics in the treatment of gastric cancer. In addition, CDC25B has proven to be an effective target for investigation and development of new therapeutic strategies for this malignancy.

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Bound polyphenol extracted from jujube pulp triggers mitochondria-mediated apoptosis and cell cycle arrest of HepG2 cell in vitro and in vivo

Journal of Functional Foods ◽

10.1016/j.jff.2018.12.017 ◽

2019 ◽

Vol 53 ◽

pp. 187-196 ◽

Cited By ~ 2

Author(s):

Shuhua Shan ◽

Yue Xie ◽

Huiling Zhao ◽

Jinping Niu ◽

Sheng Zhang ◽

...

Keyword(s):

Cell Cycle ◽

Cell Cycle Arrest ◽

Hepg2 Cell ◽

Cycle Arrest

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Growth Suppression by Acute PromyelocyticLeukemia-Associated Protein PLZF Is Mediated by Repression ofc-mycExpression

Molecular and Cellular Biology ◽

10.1128/mcb.23.24.9375-9388.2003 ◽

2003 ◽

Vol 23 (24) ◽

pp. 9375-9388 ◽

Cited By ~ 99

Author(s):

Melanie J. McConnell ◽

Nathalie Chevallier ◽

Windy Berkofsky-Fessler ◽

Jena M. Giltnane ◽

Rupal B. Malani ◽

...

Keyword(s):

Cell Cycle ◽

Cell Growth ◽

Cell Cycle Arrest ◽

Target Genes ◽

Ectopic Expression ◽

Growth Suppression ◽

Quiescent State ◽

Cycle Arrest

ABSTRACT The transcriptional repressor PLZF was identified by its translocation with retinoic acid receptor alpha in t(11;17) acute promyelocytic leukemia (APL). Ectopic expression of PLZF leads to cell cycle arrest and growth suppression, while disruption of normal PLZF function is implicated in the development of APL. To clarify the function of PLZF in cell growth and survival, we used an inducible PLZF cell line in a microarray analysis to identify the target genes repressed by PLZF. One prominent gene identified was c-myc. The array analysis demonstrated that repression of c-myc by PLZF led to a reduction in c-myc-activated transcripts and an increase in c-myc-repressed transcripts. Regulation of c-myc by PLZF was shown to be both direct and reversible. An interaction between PLZF and the c-myc promoter could be detected both in vitro and in vivo. PLZF repressed the wild-type c-myc promoter in a reporter assay, dependent on the integrity of the binding site identified in vitro. PLZF binding in vivo was coincident with a decrease in RNA polymerase occupation of the c-myc promoter, indicating that repression occurred via a reduction in the initiation of transcription. Finally, expression of c-myc reversed the cell cycle arrest induced by PLZF. These data suggest that PLZF expression maintains a cell in a quiescent state by repressing c-myc expression and preventing cell cycle progression. Loss of this repression through the translocation that occurs in t(11;17) would have serious consequences for cell growth control.

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