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 p21 cip1 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 NAOinduced 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.

Natural Compounds as Modulators of Cell Cycle Arrest: Application for Anticancer Chemotherapies

“…The fresh rhizome of Zingiber zerumbet (L.) Roscoe ex Smith (Zingiberaceae) was found to serve as source of zerumbone, which was shown to induce G2/M cell cycle arrest in human promyelocytic leukemia HL-60 cells by decreasing the cyclin B1 and CDK1 protein levels, as described elsewhere [196]. Natural antioxidant derived from spinach extract was found to exert anti-proliferative effect on human prostate cancer PC3 cells [197]. Polyphenols derived from the spinach extract were shown to increase the protein levels of CDKN1A (p21), and decrease levels of cyclin A and CDK2 proteins, as described in [197].…”

“…Natural antioxidant derived from spinach extract was found to exert anti-proliferative effect on human prostate cancer PC3 cells [197]. Polyphenols derived from the spinach extract were shown to increase the protein levels of CDKN1A (p21), and decrease levels of cyclin A and CDK2 proteins, as described in [197]. At the same time spinach extract polyphenols decreased the phosphorylated RB protein level, and total protein levels of retinoblastoma-like 1 (p107, also known as RBL1), and E2F1 transcription factor, as indicated in [197].…”

Synergistic activity between a spinach-derived natural antioxidant (NAO) and commercial antioxidants in a variety of oxidation systems

“…We found that NAO induced G1 delay and cell cycle prolongation through downregulation of the protein expression of ppRb and E2F in the human PCA cell line, PC3 (Bakshi et al, 2004).…”

“…NAO exhibits unique properties that make it an especially effective free radical scavenger (Bergman, Perelman, Dubinsky, & Grossman, 2003;Bergman et al, 2001; Ben Shaul, with strong antimutagenic potential and anti-inflammatory properties (Bakshi, Bergman, Dovrat, & Grossman, 2004;Lomnitski et al, 2003;Nyska et al, 2001Nyska et al, , 2003. Its efficiency was tested and proven in a variety of biological systems in vivo and in vitro (Breitbart et al, 2001;Lomnitski et al, 2000aLomnitski et al, , 2000bLomnitski et al, , 2003Nyska et al, 2001Nyska et al, , 2003.…”

Spinach and Health

“…β-carotene, violaxanthin, neox anthin, lutein, and phenolic acid) [29][30][31][32][33][34]. These antioxidant compounds or extracts including polyphenols, such as natural anti oxidants (NAO) [34,35] of spinach, are related to disease prevention, including cancer [31,36]. Moreover, an epidemiological study suggested that spinach is associated with reduced cancer risk [37,38].…”