Unique natural antioxidants (NAOs) and derived purified components inhibit cell cycle progression by downregulation of ppRb and E2F in human PC3 prostate cancer cells.

Abstract	Prostate cancer (PCA) is the leading cause of cancer mortality among older men in Western countries. Epidemiological studies have shown correlation between a lower risk of PCA and a higher consumption of antioxidants. However, the mechanism by which antioxidants exert their effects is still unknown. In the present study, we explored the signaling mechanism through which unique natural antioxidant derived from spinach extract (NAO) exerts their beneficial effects in the chemoprevention of PCA using human PC3 cells. Probing into the effect of NAO and its derived polyphenols on cell-cycle G1 arrest, we found that they cause cell-cycle prolongation. NAO and its two derived purified components exhibited a significant increase in the level of p21cip1 expression after 36 h of starvation, followed by 18 h of treatment with NAO in the presence of serum. In addition, under similar conditions, the expressed level of Cyclin A and CDK-2 in the PC3 cells was significantly reduced after treatment with NAO or its purified components. Immunoblot analysis demonstrated a significant increase in the hypophosphorylated form of pRb and a decrease in ppRb. NAO and its purified derived components were found to downregulate the protein expression of another member of the pRb family, p107, as well as that of E2F-1. These results suggest that NAO-induced G1 delay and cell cycle prolongation are caused by downregulation of the protein expression of ppRb and E2F in the human PCA cell line PC3.
Authors	Shlomo Bakshi, Margalit Bergman, Sara Dovrat, Shlomo Grossman
Journal	FEBS letters (FEBS Lett) Vol. 573 Issue 1-3 Pg. 31-7 (Aug 27 2004) ISSN: 0014-5793 [Print] England
PMID	15327971 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Antioxidants CDKN1A protein, human Cell Cycle Proteins Cyclin A Cyclin-Dependent Kinase Inhibitor p21 Cyclins DNA-Binding Proteins E2F Transcription Factors E2F1 Transcription Factor E2F1 protein, human Flavonoids Phenols Plant Extracts Polyphenols Retinoblastoma Protein Transcription Factors CDC2-CDC28 Kinases CDK2 protein, human Cyclin-Dependent Kinase 2
Topics	Antioxidants (pharmacology) CDC2-CDC28 Kinases (metabolism) Cell Cycle (drug effects) Cell Cycle Proteins (metabolism) Cell Division (drug effects) Cell Line, Tumor Cell Survival (drug effects) Cyclin A (metabolism) Cyclin-Dependent Kinase 2 Cyclin-Dependent Kinase Inhibitor p21 Cyclins (metabolism) DNA-Binding Proteins (metabolism) Dose-Response Relationship, Drug Down-Regulation (drug effects) E2F Transcription Factors E2F1 Transcription Factor Flavonoids (isolation & purification, pharmacology) G1 Phase (drug effects) Humans Male Phenols (isolation & purification, pharmacology) Phosphorylation (drug effects) Plant Extracts (chemistry) Polyphenols Prostatic Neoplasms (metabolism, pathology) Retinoblastoma Protein (metabolism) S Phase (drug effects) Spinacia oleracea (chemistry) Transcription Factors (metabolism)

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