Document Detail

Exogenous cysteine and cystine promote cell proliferation in CaCo-2 cells.
MedLine Citation:
PMID:  11952646     Owner:  NLM     Status:  MEDLINE    
Previous studies have shown that intracellular glutathione, a ubiquitous intracellular thiol, is related to cell proliferation and that cysteine or its disulphide form, cystine, also induces cell proliferation. Cysteine is a thiol containing amino acid and a rate-limiting precursor of glutathione. Therefore, it is still unresolved as to whether the proliferative effect of cysteine or cystine is entirely mediated by a change in the intracellular glutathione status. The objective of this study was to delineate the relationship among cysteine/cystine (thereafter referred to as cyst(e)ine), intracellular glutathione and cell proliferation in the human colon cancer CaCo-2 cell line. CaCo-2 cells were cultured in cyst(e)ine-free Dulbecco's Modified Eagle Medium without serum, and treated with 200 microm cysteine and/or 200-400 microm cystine for 24 h. In the presence of DL-buthionine-[S, R]-sulfoximine (BSO), a glutathione synthesis inhibitor, exogenously administered cyst(e)ine did not change the intracellular glutathione content, but increased the intracellular cysteine as well as cystine level. Addition of exogenous cyst(e)ine following 5 mm BSO treatment significantly increased cell proliferation as measured by 3H-thymidine incorporation and protein content. Cell cycle analyses revealed that cyst(e)ine promoted cell progression from the G1 phase to the S phase. Correspondingly, cyst(e)ine treatment induced expression of cyclin D1 and phosphorylation of retinoblastoma protein (Rb). In conclusion, these data indicate that both cysteine and cystine have proliferative effects in CaCo-2 cells independent of an increase in intracellular glutathione. Induction of cyclin D1, phosphorylation of Rb, and subsequent facilitation of G1-to-S phase transition were involved in the proliferative effect of exogenous cyst(e)ine.
T Noda; R Iwakiri; K Fujimoto; C A Rhoads; T Y Aw
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Cell proliferation     Volume:  35     ISSN:  0960-7722     ISO Abbreviation:  Cell Prolif.     Publication Date:  2002 Apr 
Date Detail:
Created Date:  2002-04-15     Completed Date:  2002-05-02     Revised Date:  2014-09-14    
Medline Journal Info:
Nlm Unique ID:  9105195     Medline TA:  Cell Prolif     Country:  England    
Other Details:
Languages:  eng     Pagination:  117-29     Citation Subset:  IM    
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MeSH Terms
Antimetabolites / pharmacology
Blotting, Western
Buthionine Sulfoximine / pharmacology
Caco-2 Cells
Chromatography, High Pressure Liquid
Cyclin D1 / metabolism
Cysteine / analysis,  pharmacology*
Cystine / analysis,  pharmacology*
Flow Cytometry
G1 Phase / drug effects*
Glutathione / analysis,  biosynthesis
Glutathione Disulfide / analysis,  metabolism
Retinoblastoma Protein / metabolism
S Phase / drug effects*
Grant Support
Reg. No./Substance:
0/Antimetabolites; 0/Retinoblastoma Protein; 136601-57-5/Cyclin D1; 48TCX9A1VT/Cystine; 5072-26-4/Buthionine Sulfoximine; GAN16C9B8O/Glutathione; K848JZ4886/Cysteine; ULW86O013H/Glutathione Disulfide

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