Document Detail

Beryllium sulfate induces p21 CDKN1A expression and a senescence-like cell cycle arrest in susceptible cancer cell types.
MedLine Citation:
PMID:  20549306     Owner:  NLM     Status:  MEDLINE    
In fibroblasts, beryllium salt causes activation of the p53 transcription factor and induction of a senescence-like state. It is not known whether Be(2+) can affect the proliferation of cancer cells, which are generally unsusceptible to senescence. A172 glioblastoma and RKO colon carcinoma cell lines each have wildtype p53, so these cell types have the potential to be responsive to agents that activate p53. In A172 cells, BeSO(4) produced a G(0)/G(1)-phase cell cycle arrest and increased expression of senescence-associated β-galactosidase, an enzymatic marker of senescence. BeSO(4) caused phosphorylation of serine-15 of p53, accumulation of p53 protein, and expression of p21, the cyclin-dependent kinase inhibitor that is prominent during senescence. BeSO(4) inhibited A172 growth with an IC(50) = 4.7 μM in a 6-day proliferation assay. In contrast, BeSO(4) had no effect on RKO cells, even though Be(2+) uptake was similar for the two cell types. This differential responsiveness marks BeSO(4) as a reagent capable of activating a separable branch of the p53 signaling network. A172 and RKO cells are known to exhibit p53-dependent upregulation of p21 in response to DNA damage. The RKO cells produced high levels of p21 when exposed to DNA damaging agents, yet failed to express p21 when treated with BeSO(4). Conversely, BeSO(4) did not cause DNA damage in A172 cells, yet it was a potent inducer of p21 expression. These observations indicate that the growth control pathway affected by BeSO(4) is distinct from the DNA damage response pathway, even though both ultimately converge on p53 and p21.
Priyatham Gorjala; Ronald K Gary
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2010-06-12
Journal Detail:
Title:  Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine     Volume:  23     ISSN:  1572-8773     ISO Abbreviation:  Biometals     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-11-09     Completed Date:  2011-02-24     Revised Date:  2013-05-29    
Medline Journal Info:
Nlm Unique ID:  9208478     Medline TA:  Biometals     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  1061-73     Citation Subset:  IM    
Department of Chemistry, University of Nevada Las Vegas, 4505 Maryland Parkway, Las Vegas, NV 89154-4003, USA.
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MeSH Terms
Beryllium / metabolism,  pharmacology*
Cell Aging / drug effects*
Cell Cycle / drug effects
Cell Line, Tumor
Cell Proliferation / drug effects
Colonic Neoplasms / physiopathology
Cyclin-Dependent Kinase Inhibitor p21 / biosynthesis*
Genes, p53 / drug effects
Glioblastoma / physiopathology
Tumor Suppressor Protein p53 / metabolism*
beta-Galactosidase / biosynthesis
Grant Support
P20 RR-016464/RR/NCRR NIH HHS; P20 RR016464-077332/RR/NCRR NIH HHS
Reg. No./Substance:
0/Cyclin-Dependent Kinase Inhibitor p21; 0/Tumor Suppressor Protein p53; 01UQ1KPC7E/beryllium sulfate; 7440-41-7/Beryllium; EC

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