ArticleBMC cancer2011
Genistein inhibits proliferation of colon cancer cells by attenuating a negative effect of epidermal growth factor on tumor suppressor FOXO3 activity.
Article in BMC cancer, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01985763 (Genistein Combined With FOLFOX or FOLFOX-Avastin for Treatment of Metastatic Colorectal Cancer), which is not on this map. Cited by 59 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Genistein Combined With FOLFOX or FOLFOX-Avastin for Treatment of Metastatic Colorectal Cancer: Phase I/II Pilot Study
Who cites it
59 citing papers in PubMed, 1 synthesis or guideline pooled it, 113 citations in OpenAlex.
- Intricate roles of estrogen and estrogen receptors in digestive system cancers: a systematic review.Cancer biology & medicine · 2024Pooled it
- Article
- Genistein as a Chemo-modulatory Agent: Exploring its Potential in Chemosensitization and Combinatorial Therapeutic Strategies for Cancer Treatment.Current topics in medicinal chemistry · 2025Review
- Role of Phytochemicals in Treatment of Aging and Cancer: Focus on Mechanism of FOXO3 Activation.Antioxidants (Basel, Switzerland) · 2024Review
- Dietary risk factors for colorectal cancer in Uganda: a case-control study.BMC nutrition · 2024Article
- Interactions between genistein and Wnt pathway in colon adenocarcinoma and early embryos.Heliyon · 2024Article
- Review
- Genistein Enhances TRAIL-Mediated Apoptosis Through the Inhibition ofTurkish journal of pharmaceutical sciences · 2024Article
- Implications of estrogen and its receptors in colorectal carcinoma.Cancer medicine · 2023Review
- KCNK9 mediates the inhibitory effects of genistein on hepatic metastasis from colon cancer.Clinics (Sao Paulo, Brazil) · 2023Article
- Evaluation of the Effects of Genistein In Vitro as a Chemopreventive Agent for Colorectal Cancer-Strategy to Improve Its Efficiency When Administered Orally.Molecules (Basel, Switzerland) · 2022Article
- Review
- The Preparation of Gen-NHPharmaceutics · 2022Article
- Exploring the recent trends in perturbing the cellular signaling pathways in cancer by natural products.Frontiers in pharmacology · 2022Review
- Nutraceuticals and Cancer: Potential for Natural Polyphenols.Nutrients · 2021Review
- Genistein Directly Represses the Phosphorylation of STAT5 in Lactating Mammary Epithelial Cells.ACS omega · 2021Article
- Transcription factors in colorectal cancer: molecular mechanism and therapeutic implications.Oncogene · 2021Review
- Targeting STAT proteins via computational analysis in colorectal cancer.Molecular and cellular biochemistry · 2021Article
- Genistein: An Integrative Overview of Its Mode of Action, Pharmacological Properties, and Health Benefits.Oxidative medicine and cellular longevity · 2021Review
- Targeting estrogen receptors in colorectal cancer.Molecular biology reports · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundSoy consumption is associated with a lower incidence of colon cancer which is believed to be mediated by one of its of components, genistein. Genistein may inhibit cancer progression by inducing apoptosis or inhibiting proliferation, but mechanisms are not well understood. Epidermal growth factor (EGF)-induced proliferation of colon cancer cells plays an important role in colon cancer progression and is mediated by loss of tumor suppressor FOXO3 activity. The aim of this study was to assess if genistein exerts anti-proliferative properties by attenuating the negative effect of EGF on FOXO3 activity.
methodsThe effect of genistein on proliferation stimulated by EGF-mediated loss of FOXO3 was examined in human colonic cancer HT-29 cells. EGF-induced FOXO3 phosphorylation and translocation were assessed in the presence of genistein. EGF-mediated loss of FOXO3 interactions with p53 (co-immunoprecipitation) and promoter of p27kip1 (ChIP assay) were examined in presence of genistein in cells with mutated p53 (HT-29) and wild type p53 (HCT116). Silencing of p53 determined activity of FOXO3 when it is bound to p53.
resultsGenistein inhibited EGF-induced proliferation, while favoring dephosphorylation and nuclear retention of FOXO3 (active state) in colon cancer cells. Upstream of FOXO3, genistein acts via the PI3K/Akt pathway to inhibit EGF-stimulated FOXO3 phosphorylation (i.e. favors active state). Downstream, EGF-induced disassociation of FOXO3 from mutated tumor suppressor p53, but not wild type p53, is inhibited by genistein favoring FOXO3-p53(mut) interactions with the promoter of the cell cycle inhibitor p27kip1 in colon cancer cells. Thus, the FOXO3-p53(mut) complex leads to elevated p27kip1 expression and promotes cell cycle arrest.
conclusionThese novel anti-proliferative mechanisms of genistein suggest a possible role of combining genistein with other chemoreceptive agents for the treatment of colon cancer.
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