Effects of selenite and genistein on G2/M cell cycle arrest and apoptosis in human prostate cancer cells

Rui Zhao; Nong Xiang; Fredrick E Domann; Weixiong Zhong

doi:10.1080/01635580802582751

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Effects of selenite and genistein on G2/M cell cycle arrest and apoptosis in human prostate cancer cells

Journal article

Open access

Peer reviewed

Effects of selenite and genistein on G2/M cell cycle arrest and apoptosis in human prostate cancer cells

Rui Zhao, Nong Xiang, Fredrick E Domann and Weixiong Zhong

Nutrition and cancer, Vol.61(3), pp.397-407

2009

DOI: 10.1080/01635580802582751

PMCID: PMC2724066

PMID: 19373614

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https://www.ncbi.nlm.nih.gov/pmc/articles/2724066View

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Abstract

Combination of chemopreventive agents with distinct molecular mechanisms is considered to offer a potential for enhancing cancer prevention efficacy while minimizing toxicity. Here we report two chemopreventive agents, selenite and genistein, that have synergistic effects on apoptosis, cell cycle arrest, and associated signaling pathways in p53-expressing LNCaP and p53-null PC3 prostate cancer cells. We show that selenite induced apoptosis only, whereas genistein induced both apoptosis and G2/M cell cycle arrest. Combination of these two agents exhibited enhanced effects, which were slightly greater in LNCaP than PC3 cells. Selenite or genistein alone upregulated protein levels of p53 in LNCaP cells only and p21(waf1) and Bax in both cell lines. Additionally, genistein inhibited AKT phosphorylation. Downregulation of AKT by siRNA caused apoptosis and G2/M cell cycle arrest and masked the effects of genistein. Treatment with insulin-like growth factor I (IGF-I) elevated levels of total and phosphorylated AKT and suppressed the effects of genistein. Neither downregulation of AKT nor IGF-I treatment altered the cellular effects of selenite. Our study demonstrates that selenium and genistein act via different molecular mechanisms and exhibit enhanced anticancer effects, suggesting that a combination of selenium and genistein may offer better efficacy and reduction of toxicity in prostate cancer prevention.

Prostatic Neoplasms - pathology

Insulin-Like Growth Factor I - pharmacology

Apoptosis - drug effects

Humans

Male

Proto-Oncogene Proteins c-akt - physiology

Sodium Selenite - pharmacology

Cell Division - drug effects

G2 Phase - drug effects

Dose-Response Relationship, Drug

Tumor Suppressor Protein p53 - physiology

Genistein - pharmacology

Cell Line, Tumor

Prostatic Neoplasms - prevention & control

Anticarcinogenic Agents - pharmacology

Prostatic Neoplasms - drug therapy

Details

Title: Subtitle: Effects of selenite and genistein on G2/M cell cycle arrest and apoptosis in human prostate cancer cells
Creators: Rui Zhao - Department of Pathology and Laboratory Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin 53792, USA
Nong Xiang
Fredrick E Domann
Weixiong Zhong
Resource Type: Journal article
Publication Details: Nutrition and cancer, Vol.61(3), pp.397-407
DOI: 10.1080/01635580802582751
PMID: 19373614
PMCID: PMC2724066
NLM abbreviation: Nutr Cancer
ISSN: 0163-5581
eISSN: 1532-7914
Publisher: United States
Grant note: R01 CA114281 / NCI NIH HHS R29 CA073612 / NCI NIH HHS CA114281 / NCI NIH HHS R01 CA114281-04 / NCI NIH HHS R01 CA073612-09 / NCI NIH HHS R01 CA115438-02 / NCI NIH HHS R01 CA115438 / NCI NIH HHS R01 CA073612-10 / NCI NIH HHS R01 CA114281-03 / NCI NIH HHS R01 CA115438-03 / NCI NIH HHS R56 CA073612 / NCI NIH HHS R01 CA073612 / NCI NIH HHS CA73612, / NCI NIH HHS
Language: English
Date published: 2009
Academic Unit: Pathology; Surgery; Radiation Oncology
Record Identifier: 9984046926702771

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