Vitamin C affects G0/G1 cell cycle and autophagy by downregulating of cyclin D1 in gastric carcinoma cells

2021 ◽  
Vol 85 (3) ◽  
pp. 553-561
Author(s):  
Chenxia Ren ◽  
Cuiling Wu ◽  
Changqing Yang ◽  
Changhong Lian
Keyword(s):  
Cell Cycle ◽  
Gastric Carcinoma ◽  
Vitamin C ◽  
Cyclin D1 ◽  
Bioinformatics Analysis ◽  
Carcinoma Cells ◽  
Cell Cycle Pathway ◽  
Differential Gene ◽  
Regulation Of Cell Cycle ◽  
Amp Activated Protein Kinase

ABSTRACT Vitamin C has re-emerged as a promising anticancer agent. This study attempts to analyze the differential gene expression of profiles GSE11919 to look for some clues, and the most significant cell cycle pathway caused by vitamin C was identified by integrated bioinformatics analysis. Inspired by this, we investigated the effect of vitamin C treatment on gastric carcinoma cells by detection of cell cycle, apoptosis, and autophagy. Vitamin C significantly elevated the percentage of cells at G0/G1 phase, whereas the percentage of S phase cells was decreased. Meanwhile, vitamin C treatment resulted in downregulation of cell cycle-related protein Cyclin D1. We deduced that the downregulation of Cyclin D1 by vitamin C accompanied by significantly increased 5′AMP-activated protein kinase and induced autophagy in MKN45 cells. These results suggest that vitamin C has the antiproliferation effect on gastric carcinoma cells via the regulation of cell cycle and autophagy by Cyclin D1.

Expression of cyclin D1 and p21(WAF1/CIP1) in human gastric carcinoma and its clinicopathologic significance.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15114-e15114
Author(s):  
Vasiliki Michalaki ◽  
Theodosios Theodosopoulos ◽  
Agathi Kondi- Pafiti ◽  
Constantine G. Gennatas
Keyword(s):  
Gastric Cancer ◽  
Cell Cycle ◽  
Gastric Carcinoma ◽  
Cyclin D1 ◽  
Gastric Epithelium ◽  
Nuclear Staining ◽  
Cell Cycle Regulators ◽  
Diffuse Type ◽  
Clinicopathological Findings ◽  
P21 Waf1

e15114 Background: The deregulation of cyclin, cyclin-dependent kinases (CDKs) and their inhibitors could have a crucial role in the development of diverse human cancers. Alterations in cell cycle regulators and subsequent deregulation of the cell cycle are frequently involved in tumorigenesis and/or tumor progression. The aim of our study was to detect the abnormal expression of cyclin D1 and p21(WAF1/CIP1)in gastric carcinoma and investigate its clinicopathologic significance. Methods: Proteins of cyclin D1 were detected by immunohistochemistry in 80 cases of advanced gastric carcinoma, and 30 cases of benign gastric diseases (chronic gastritis, atrophic gastritis, gastric metaplasia, and gastric dysplasia). From each patient formaldehyde–fixed paraffin sections were stained and examined by immunohistochemistry using monoclonal antibodies.All tumor cells with distinct nuclear staining were considered positive. Results: Sixty-five patients were male and forty five female. Normal gastric epithelium showed consistently positive immunostain for p21WAF1/CIP1. Loss of p21WAF1/CIP1 expression was noted in 65% of intestinal type adenocarcinoma and in 90% of diffuse type adenocarcinoma. Overexpression of cyclin D1 was detected in 90% of advanced gastric carcinomas. Among the various clinicopathological findings, overexpression of cyclin D1 was associated with lymph-node metastasis (P=0.003) and recurrence (P=0.044). Loss of p21WAF1/CIP1 expression was more frequent in diffuse type cancers (P=0.005) and was correlated with recurrence (P=0.002) and death (P=0.001). Conclusions: These findings suggest that overexpression of cyclin D1 is a frequent finding in gastric cancer and immunohistochemical analysis for cell cycle regulators, might be a useful prognostic indicator in gastric cancer.

Pterostilbene Induces Apoptosis and Cell Cycle Arrest in Human Gastric Carcinoma Cells

2007 ◽  
Vol 55 (19) ◽  
pp. 7777-7785 ◽  
Author(s):  
Min-Hsiung Pan ◽  
Yen-Hui Chang ◽  
Vladimir Badmaev ◽  
Kalyanam Nagabhushanam ◽  
Chi-Tang Ho
Keyword(s):  
Cell Cycle ◽  
Gastric Carcinoma ◽  
Cell Cycle Arrest ◽  
Carcinoma Cells ◽  
Human Gastric Carcinoma ◽  
Cycle Arrest ◽  
Human Gastric Carcinoma Cells

scholarly journals Interferon-λ1 induces G1 phase cell cycle arrest and apoptosis in gastric carcinoma cells in vitro

2014 ◽  
Vol 32 (1) ◽  
pp. 199-204 ◽  
Author(s):  
ZHITAO GAO ◽  
MOLI ZHU ◽  
YAPING WU ◽  
PAN GAO ◽  
ZHIHAI QIN ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Gastric Carcinoma ◽  
Cell Cycle Arrest ◽  
Carcinoma Cells ◽  
Phase Cell ◽  
G1 Phase ◽  
Cycle Arrest

Alterations in the cell cycle checkpoint pathway in breast cancer.

2015 ◽  
Vol 33 (28_suppl) ◽  
pp. 126-126
Author(s):  
Gargi Dan Basu ◽  
Tracey White ◽  
Janine R LoBello ◽  
Ahmet Kurdoglu ◽  
Subha Krishnan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cyclin D1 ◽  
Exome Sequencing ◽  
Genetic Alterations ◽  
Cell Cycle Checkpoint ◽  
Her2 Status ◽  
Her2 Positive ◽  
Cell Cycle Pathway ◽  
Tnbc Subtype

126 Background: Breast cancer is a molecularly diverse disease with molecular subtypes defined by ER, PR and HER2 status. Dysregulation of the cell cycle pathway through activation of cyclin D1 and/or inactivation of CDKN2A is a mechanism of tumor progression in breast cancer and drugs targeting CDK4/6 is undergoing investigation in this disease with promising preliminary results. We investigated several key genetic alterations in cell cycle regulatory proteins in advanced breast cancer patient samples to identify potential targets for cell cycle related treatment options. Methods: A comprehensive genomic profiling was performed on 37 breast cancer samples with the majority being metastatic. Testing included targeted exome sequencing of 562 genes in tumor and paired normal DNA. Results: Patients’ ages ranged from 27-66 years. Analysis of cell cycle regulatory genes revealed focal amplification of cyclin D1/D2 or CDKN2A loss in 9/37 (24%) of cases, of which, 45% were hormone receptor (HR) positive, HER2 negative, 33% were HR positive, HER2 positive and 22% were triple negative (TNBC) subtype. Loss of RB1 was analyzed since it negatively regulates response to CDK4/6 inhibitors. Loss of RB1 was noted in 4/37 (10.8%) of cases, all of which were TNBCs. Only a single TNBC with RB1 loss had concurrent CDK4 amplification and loss of CDKN2A. No evidence of CCNE1 amplification was found in any samples. Incidence of CDK4 and CDK6 amplification was found in samples with cyclin D1 amplification or CDKN2A loss. Our cohort included a single male TNBC patient who harbored cyclin D1 amplification as well as CDKN2A loss. Overall, amplification of cyclin D1, cyclin D2, CDK4 and CDK6 was found in 16%, 5.4%, 2.7% and 2.7% respectively. Loss of CDKN2A was noted in 5.4% of tumors profiled. Conclusions: Exome sequencing identified subsets of patients with mutated cell cycle associated genes that may benefit from CDK 4/6 inhibitors. Our data suggests loss of RB1 is more frequent in TNBC subtype which may confer resistance to CDK4/6 inhibitors. Our analysis suggests that in addition to HR positive, HER2 negative patients, a subset of HR positive, HER2 positive patients could be sensitive to CDK4/6 inhibitors due to activation of the cell cycle pathway as evidenced by mutations in key genes.

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