Alterations of cell cycle control proteins SHP-1/2, p16, CDK4 and cyclin D1 in radioresistant nasopharyngeal carcinoma cells

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.

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Immunohistochemical detection of cell cycle regulators, Fhit protein and apoptotic cells in parathyroid lesions

Acta Endocrinologica ◽

10.1530/eje.0.1480081 ◽

2003 ◽

pp. 81-87 ◽

Cited By ~ 9

Author(s):

GE Thomopoulou ◽

S Tseleni-Balafouta ◽

AC Lazaris ◽

H Koutselini ◽

N Kavantzas ◽

...

Keyword(s):

Cell Cycle ◽

Cyclin D1 ◽

Cell Cycle Control ◽

Parathyroid Glands ◽

Considerable Proportion ◽

Parathyroid Cell ◽

Apoptotic Cells ◽

Cell Cycle Regulators ◽

Suppressor Activity ◽

Fhit Protein

OBJECTIVE: The pathological distinction between parathyroid neoplasms and hyperplasias remains difficult. Changes in cell cycle control may lead to clonal proliferation and precede tumorigenesis. The parathyroid adenoma 1 oncogene, subsequently identified as the gene encoding cyclin D1, has been shown to be important to parathyroid tumour development. In addition to cell proliferation, the mechanisms of parathyroid cell turnover include apoptosis. The tumour-suppressor activity of the fragile histidine triad gene (FHIT) is linked to its proapoptotic function and cell cycle control. We attempted to evaluate the cellular proliferative kinetics and apoptotic function of the parathyroid glands in patients with non-familial hyperparathyroidism (HPT). DESIGN: TIssue specimens were taken from 40 patients with primary HPT (17 adenomas, two carcinomas and 21 primary hyperplasias) and from 30 patients with secondary HPT. Normal glands served as controls. METHODS: In a standard immunohistochemical procedure, monoclonal antibodies to Ki-67 antigen and single-stranded DNA were applied to detect cycling and apoptotic cells respectively; polyclonal antibodies to cyclin D1 and Fhit protein were used. Immunostaining was estimated by image analysis and statistical analysis was subsequently performed. RESULTS: Significantly higher proliferative and apoptotic indexes were detected in the diseased glands in comparison with normal controls. In neoplastic and secondarily hyperplastic glands, apoptotic indexes were higher than in primarily hyperplastic glands; the difference between neoplastic and primarily hyperplastic glands was statistically significant (P=0.034). Cyclin D1 was overexpressed in a considerable proportion of tumours (68.4%). A reduction of Fhit protein immunoreactivity was selectively noticed in carcinomas. CONCLUSIONS: In primary hyperplasia, the remarkable proliferation of parathyroid glands may be due to the reduction of the apoptotic process. FHIT gene abnormalities are worthy of investigation in parathyroid carcinogenesis.

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Apoptosis Resistance of MCF-7 Breast Carcinoma Cells to Ionizing Radiation Is Independent of p53 and Cell Cycle Control but Caused by the Lack of Caspase-3 and a Caffeine-Inhibitable Event

Cancer Research ◽

10.1158/0008-5472.can-04-1082 ◽

2004 ◽

Vol 64 (19) ◽

pp. 7065-7072 ◽

Cited By ~ 79

Author(s):

Frank Essmann ◽

Ingo H. Engels ◽

Gudrun Totzke ◽

Klaus Schulze-Osthoff ◽

Reiner U. Jänicke

Keyword(s):

Cell Cycle ◽

Breast Carcinoma ◽

Ionizing Radiation ◽

Caspase 3 ◽

Cell Cycle Control ◽

Carcinoma Cells ◽

Apoptosis Resistance ◽

Breast Carcinoma Cells ◽

Mcf 7

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KAI1 overexpression promotes apoptosis and inhibits proliferation, cell cycle, migration, and invasion in nasopharyngeal carcinoma cells

American Journal of Otolaryngology ◽

10.1016/j.amjoto.2016.09.011 ◽

2017 ◽

Vol 38 (5) ◽

pp. 511-517 ◽

Cited By ~ 2

Author(s):

Zheng Guo ◽

Yili Wang ◽

Jing Yang ◽

Jinghua Zhong ◽

Xia Liu ◽

...

Keyword(s):

Cell Cycle ◽

Nasopharyngeal Carcinoma ◽

Carcinoma Cells ◽

Migration And Invasion

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Iron chelation regulates cyclin D1 expression via the proteasome: a link to iron deficiency–mediated growth suppression

Blood ◽

10.1182/blood-2006-10-047753 ◽

2006 ◽

Vol 109 (9) ◽

pp. 4045-4054 ◽

Cited By ~ 95

Author(s):

Effie Nurtjahja-Tjendraputra ◽

Dong Fu ◽

Juanita M. Phang ◽

Des R. Richardson

Keyword(s):

Cell Cycle ◽

Cyclin D1 ◽

Cell Cycle Control ◽

D1 Protein ◽

Iron Chelation ◽

Growth Suppression ◽

Dependent Manner ◽

Critical Function ◽

Cyclin D1 Protein

Abstract Iron (Fe) plays an important role in proliferation, and Fe deficiency results in G1/S arrest. Despite this, the precise role of Fe in cell-cycle control remains unclear. Cyclin D1 plays a critical function in G1 progression by interacting with cyclin-dependent kinases. Previously, we examined the effect of Fe depletion on the expression of cell-cycle control molecules and identified a marked decrease in cyclin D1 protein, although the mechanism involved was unknown. In this study, we showed that cyclin D1 was regulated posttranscriptionally by Fe depletion. Iron chelation of cells in culture using desferrioxamine (DFO) or 2-hydroxy-1-naphthylaldehyde isonicotinoyl hydrazone (311) decreased cyclin D1 protein levels after 14 hours and was rescued by the addition of Fe. Cyclin D1 half-life in control cells was 80 ± 15 minutes (n = 5), while in chelator-treated cells it was significantly (P < .008) decreased to 38 ± 3 minutes (n = 5). Proteasomal inhibitors rescued the Fe chelator–mediated decrease in cyclin D1 protein, suggesting the role of the proteasome. In Fe-replete cells, cyclin D1 was degraded in an ubiquitin-dependent manner, while Fe depletion induced a ubiquitin-independent pathway. This is the first report linking Fe depletion–mediated growth suppression at G1/S to a mechanism inducing cyclin D1 proteolysis.

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