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

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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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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Lobetyol activate MAPK pathways associated with G 1 /S cell cycle arrest and apoptosis in MKN45 cells in vitro and in vivo

Biomedicine & Pharmacotherapy ◽

10.1016/j.biopha.2016.03.046 ◽

2016 ◽

Vol 81 ◽

pp. 120-127 ◽

Cited By ~ 5

Author(s):

Jie Shen ◽

XinGang Lu ◽

WangChun Du ◽

Jun Zhou ◽

HongFu Qiu ◽

...

Keyword(s):

Cell Cycle ◽

Cell Cycle Arrest ◽

Mapk Pathways ◽

Cycle Arrest

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DT-13 synergistically potentiates the sensitivity of gastric cancer cells to topotecan via cell cycle arrest in vitro and in vivo

European Journal of Pharmacology ◽

10.1016/j.ejphar.2017.10.014 ◽

2018 ◽

Vol 818 ◽

pp. 124-131 ◽

Cited By ~ 9

Author(s):

Hongzhi Du ◽

Yang Liu ◽

Xudong Chen ◽

Xiaowen Yu ◽

Xiaoying Hou ◽

...

Keyword(s):

Gastric Cancer ◽

Cell Cycle ◽

Cell Cycle Arrest ◽

Cancer Cells ◽

Gastric Cancer Cells ◽

Cycle Arrest

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Abstract C36: Dc917 inhibits the growth of mouse lung carcinoma both in vitro and in vivo through cell cycle arrest and ERK signaling pathway

10.1158/1538-7445.fbcr11-c36 ◽

2011 ◽

Author(s):

Hang Dong ◽

Zhihong Jiang ◽

Vincent Kam Wai Wong ◽

Hua Zhou ◽

Liang Liu

Keyword(s):

Cell Cycle ◽

Cell Cycle Arrest ◽

Signaling Pathway ◽

Lung Carcinoma ◽

Erk Signaling ◽

Mouse Lung ◽

Cycle Arrest

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Anti-CD19 inhibits the growth of human B-cell tumor lines in vitro and of Daudi cells in SCID mice by inducing cell cycle arrest

Blood ◽

10.1182/blood.v83.5.1329.1329 ◽

1994 ◽

Vol 83 (5) ◽

pp. 1329-1336 ◽

Cited By ~ 56

Author(s):

MA Ghetie ◽

LJ Picker ◽

JA Richardson ◽

K Tucker ◽

JW Uhr ◽

...

Keyword(s):

Cell Cycle ◽

B Cell ◽

Cell Cycle Arrest ◽

Inhibitory Effect ◽

Scid Mice ◽

Cell Tumor ◽

Cycle Arrest ◽

A Chain

Abstract In this report, we extend our previous findings that IgG or F(ab′)2 fragments of HD37 anti-CD19 antibody (Ab) in combination with the immunotoxin (IT), RFB4-anti-CD22-deglycosylated ricin A chain (dgA) (but neither reagent alone), prolonged the survival of SCID mice with disseminated human Daudi lymphoma (SCID/Daudi mice) to 1 year at which time they still remained tumor-free. We explored the mechanisms by which the HD37 Ab exerts antitumor activity in vivo by studying its activity in vitro. We found that it has antiproliferative activity (IC50 = 5.2 - 9.8 x 10(-7) mol/L) on three CD19+ Burkitt's lymphoma cell lines (Daudi, Raji, and Namalwa) but not on a weakly CD19-positive (CD19lo) pre-B cell tumor (Nalm-6). The inhibitory effect was manifested by cell cycle arrest, but not apoptosis. Results using three additional anti-CD19 Abs, suggest that the affinity of the antibody and possibly the epitope which it recognizes may effect its capacity to transmit a signal that induces cell cycle arrest. Hence, therapeutically useful Abs may exert anti-tumor activity by a variety of mechanisms, each of which should be evaluated before undertaking clinical trials in humans.

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Evaluation of anticancer activity in vitro and in vivo of iridium(iii) polypyridyl complexes

New Journal of Chemistry ◽

10.1039/c9nj01001g ◽

2019 ◽

Vol 43 (22) ◽

pp. 8566-8579 ◽

Cited By ~ 5

Author(s):

Miao He ◽

Qiao-Yan Yi ◽

Wen-Yao Zhang ◽

Lan Bai ◽

Fan Du ◽

...

Keyword(s):

Cell Cycle ◽

Membrane Potential ◽

Cytotoxic Activity ◽

Anticancer Activity ◽

Cell Cycle Arrest ◽

Mitochondrial Membrane ◽

Polypyridyl Complexes ◽

Cycle Arrest

Three new iridium(iii) polypyridyl complexes were synthesized. The cytotoxic activity in vitro and in vivo, apoptosis, cell cycle arrest, mitochondrial membrane potential, ROS and the expression of Bcl-2 family proteins were investigated.

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