The antiproliferative effect of beta-carotene requires p21waf1/cip1 in normal human fibroblasts.
Eur J Biochem
; 267(8): 2290-6, 2000 Apr.
Article
in En
| MEDLINE
| ID: mdl-10759853
ABSTRACT
In normal human fibroblasts, beta-carotene induces a cell-cycle delay in the G1 phase independent of its provitamin A activity via a mechanism not yet elucidated. In this study we provide biochemical evidence showing that delayed progression through the G1 phase occurs concomitantly with an increase in both nuclear-bound and total p21waf1/cip1 protein levels; an increase in the amount of p21waf1/cip1 associated with cdk4; the inhibition of cyclin D1-associated cdk4 kinase activity; and a reduction in the levels of hyperphosphorylated forms of retinoblastoma protein, and particularly, in phosphorylated Ser780. The role of p21waf1/cip1 in the antiproliferative effect of the carotenoid was further supported by genetic evidence that neither changes in cell-cycle progression nor in the phosphorylation status of retinoblastoma protein were observed in p21waf1/cip1-deficient human fibroblasts treated with beta-carotene. These results clearly demonstrate that p21waf1/cip1 is involved directly in the molecular pathway by which beta-carotene inhibits cell-cycle progression.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Proto-Oncogene Proteins
/
Cyclins
/
Beta Carotene
Limits:
Humans
Language:
En
Journal:
Eur J Biochem
Year:
2000
Document type:
Article
Affiliation country:
Italy