p53-independent Induction of p21 (WAF1/CIP1), Reduction of Cyclin B1 and G2/M Arrest by the Isoflavone Genistein in Human Prostate Carcinoma Cells
Open accessAbstract
Genistein, a natural isoflavonoid phytoestrogen, is a strong inhibitor of protein tyrosine kinase and DNA topoisomerase II activities. Genistein has been shown to have anticancer proliferation, differentiation and chemopreventive effects. In the present study, we have addressed the mechanism of action by which genistein suppressed the proliferation of p53‐null human prostate carcinoma cells. Genistein significantly inhibited the cell growth, which effect was reversible, and induced dendritelike structure. The inhibitory effects of genistein on cell growth proliferation were associated with a G2/M arrest in cell cycle progression concomitant with a marked inhibition of cyclin B1 and an induction of Cdk inhibitor p21 (WAF1/CIP1) in a p53‐independent manner. Following genistein treatment of cells, an increased binding of p21 with Cdk2 and Cdc2 paralleled a significant decrease in Cdc2 and Cdk2 kinase activity with no change in Cdk2 and Cdc2 expression. Genistein also induced the activation of a p21 promoter reporter construct, utilizing a sequence distinct from the p53‐binding site. Analysis of deletion constructs of the p21 promoter indicated that the response to genistein could be localized to the 300 base pairs proximal to the transcription start site. These data suggest that genistein may exert a strong anticarcinogenic effect, and that this effect possibly involves an induction of p21, which inhibits the threshold kinase activities of Cdks and associated cyclins, leading to a G2/M arrest in the cell cycle progression.
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In vitro studies have demonstrated that genistein may exert effects on cancer risk through promoting cell-cycle arrest, inducing apoptosis, and reducing cancer cell migration.
“Further in vitro studies have demonstrated that genistein may exert effects on cancer risk through promoting cell-cycle arrest [137] inducing apoptosis [138] and reducing cancer cell migration [139].”
From Fermented foods: definitions and characteristics, impact on the gut microbiota and effects on gastrointestinal health and disease (2019) · cites this paper as [137]
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Dimidi, E., Cox, S., Rossi, M., & Whelan, K. (2019) · Nutrients · doi:10.3390/nu11081806 · Cited by 801 · see citing works
- Authors
- Choi, Y. H., Lee, W. H., Park, K., & Zhang, L.
- Affiliations
- Georgetown University Medical Center (US)
- Pusan National University (KR)
- National Institutes of Health (US)
- Corresponding author
- Park, Kun‐Young
- Venue
- Japanese Journal of Cancer Research
- Publisher
- Wiley
- Published
- 2000-02
- Volume
- 91
- Issue
- 2
- Pages
- 164-173
- ISSN
- 0910-5050 (ISSN-L)
- PMC
- PMC5926325
- OpenAlex
- W1983937756
- Cited by
- 164
- References
- 60
- Citations by year
- 2026: 2 · 2024: 2 · 2023: 3 · 2022: 2 · 2021: 1 · 2020: 4 · 2019: 9 · 2018: 2 · 2017: 5 · 2016: 1 · 2015: 9 · 2014: 3 · 2013: 10 · 2012: 6
- FWCI
- 8.23
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Japanese Journal of Cancer Research (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Phytoestrogen effects and research
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Keywords
- genistein, isoflavones, prostate cancer, p21, cyclin B1, G2/M cell cycle arrest, p53-independent pathway, cyclin-dependent kinase inhibition, cdc2 kinase, p21 promoter, anticancer activity, p53-null cells
- MeSH terms
- Cell Division, Humans, Male, Mitosis, Promoter Regions, Genetic, Prostatic Neoplasms, RNA, Messenger, Tumor Cells, Cultured, Tumor Suppressor Protein p53, G2 Phase, CDC2 Protein Kinase, Cyclins, Anticarcinogenic Agents, Protein Serine-Threonine Kinases, Cyclin-Dependent Kinases, Genistein, Cyclin B, CDC2-CDC28 Kinases, Cyclin-Dependent Kinase Inhibitor p21, Cyclin-Dependent Kinase 2, Cyclin B1
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