Duchesnea Phenolic Fraction Inhibits In Vitro and In Vivo Growth of Cervical Cancer Through Induction of Apoptosis and Cell Cycle Arrest

Human menstrual blood-derived stem cells (hMBSCs) are a novel type of mesenchymal stem cells (MSCs) that have a high proliferative rate, multilineage differentiation potential, low immunogenicity, and low oncogenicity, making them suitable candidates for regenerative medicine. The therapeutic efficacy of hMBSCs has been demonstrated in some diseases; however, their effects on cervical cancer remain unclear. In the present study, we investigated whether hMBSCs have anticancer properties on cervical cancer cells in vivo and in vitro, which has not yet been reported. In vitro, transwell coculturing experiments revealed that hMBSCs suppress the proliferation and invasion of HeLa cervical cancer cells by inducing G0/G1 cell cycle arrest. In vivo, we established a xenografted BALB/c nude mouse model by subcutaneously coinjecting HeLa cells with hMBSCs for 21 days. We found that hMBSCs significantly decrease the average volume and average weight of xenografted tumors. ELISA, TGF-β1 antibody, and recombinant human TGF-β1 (rhTGF-β1) were used to analyze whether TGF-β1 contributed to cell cycle arrest. We found that hMBSC-secreted TGF-β1 and rhTGF-β1 induced cell cycle arrest and increased the expression of phospho-JNK and phospho-P21 in HeLa cells, which was mostly reversed by TGF-β1 antibody. These results indicate that hMBSCs have antitumor properties on cervical cancer in vitro and in vivo, mediated by the TGF-β1/JNK/p21 signaling pathway. In conclusion, this study suggests that hMBSC-based therapy is promising for the treatment of cervical cancer.

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Aloperine executes antitumor effects through the induction of apoptosis and cell cycle arrest in prostate cancer in vitro and in vivo

OncoTargets and Therapy ◽

10.2147/ott.s165262 ◽

2018 ◽

Vol Volume 11 ◽

pp. 2735-2743 ◽

Cited By ~ 13

Author(s):

Zhixin Ling ◽

Han Guan ◽

Zonghao You ◽

Can Wang ◽

Ling Hu ◽

...

Keyword(s):

Prostate Cancer ◽

Cell Cycle ◽

Cell Cycle Arrest ◽

Antitumor Effects ◽

Cycle Arrest ◽

Induction Of Apoptosis

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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

Journal of Biochemical and Molecular Toxicology ◽

10.1002/jbt.22831 ◽

2021 ◽

Author(s):

Shuai Man ◽

Zhuzhu Wu ◽

Rui Sun ◽

Qi Guan ◽

Zengqiang Li ◽

...

Keyword(s):

Cell Cycle ◽

Cell Cycle Arrest ◽

M Cell ◽

Cycle Arrest

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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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