p53, mutations, and apoptosis in genistein-exposed human lymphoblastoid cells

Morris, Suzanne M.

doi:10.1016/s0027-5107(98)00126-2

Cited by 53 publications

(21 citation statements)

References 60 publications

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“…Apoptosis has already been proposed as one of the candidate pathways by which phytoestrogen might inhibit growth because both daidzein and biochanin A have been shown to induce condensed chromosomes in MCF-7 cells as revealed by acridine orange staining [33]. Moreover, further evidence for the involvement of P53 in cell cycle arrest has been provided by Morris et al [22], who reported that the wild type P53 protein is essential for apoptosis to be induced immediately after exposure to the phytoestrogen genistein. In our study, human breast cancer cells T-47D treated with biochanin A or daidzein showed elevated protein levels of P53.…”

Section: Discussionmentioning

confidence: 97%

“…The tumor suppressor protein P53, which is commonly inactivated in tumors, is a major regulator of cell cycle progression in response to DNA damage or arrest of DNA synthesis [4,9,10,17,22]. Apoptosis has already been proposed as one of the candidate pathways by which phytoestrogen might inhibit growth because both daidzein and biochanin A have been shown to induce condensed chromosomes in MCF-7 cells as revealed by acridine orange staining [33].…”

Section: Discussionmentioning

confidence: 99%

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Growth and cell cycle regulation by isoflavones in human breast carcinoma cells

et al. 2002

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antiestrogen-like activities [20,21]. In recent years, isoflavones have attracted much attention because of their possible cancer-preventing effects for certain cancers. It has been observed that Asian women who consume a traditional low-fat high-soy diet have a lower risk of developing breast cancer, INTRODUCTIONIsoflavones are a group of chemicals present in plants and foliage. The structural similarity of isoflavones to natural animal estrogens has suggested that this group of chemicals may exhibit certain estrogen-or Original articleGrowth and cell cycle regulation by isoflavones in human breast carcinoma cells Abstract -The isoflavones daidzein and biochanin A induced a biphasic growth response in T-47D human breast cancer cells. At growth stimulatory concentrations, daidzein increased the percentage of cells entering the S phase, while at a growth inhibitory concentration, daidzein obstructed the progression of the cell cycle in the G2/M phase. Biochanin A regulated the cell cycle progression in a similar manner and showed a delay in the progression from the S phase to the G2/M phase at growth inhibitory concentrations. The levels of a cell cycle regulatory protein, P53, in response to the treatment of isoflavones, were also determined. Cells that became de-attached and floated in the medium after treatment with growth inhibitory concentrations of daidzein or biochanin A, showed higher P53 levels than cells that remained attached. These results suggest that daidzein and biochanin A influence T-47D cell proliferation and cell cycle progression, and that the underlying mechanisms might be associated with the P53 protein levels.isoflavones / cell cycle / P53 / breast cancer cells Reprod. Nutr. Dev. 42 (2002) 55-64 55

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Growth and cell cycle regulation by isoflavones in human breast carcinoma cells

et al. 2002

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“…HPV infections are often transient; however, persistent infections, especially with oncogenic or high-risk HPV types (e.g. , further increase the likelihood of developing cervical cancer (2). HPV-induced oncogenesis in cervical carcinoma is largely attributable to expression of the viral oncoproteins E6 and E7, but HPV infection alone is insufficient to induce malignant transformation of cervical epithelium.…”

Section: Introductionmentioning

confidence: 99%

WIF1 is a frequent target for epigenetic silencing in squamous cell carcinoma of the cervix

et al. 2011

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Aberrant activation of the Wnt/b-catenin signaling axis is a prominent oncogenic mechanism in numerous cancers including cervical cancer. Wnt inhibitory factor-1 (WIF1) is a secreted protein that binds Wnt and antagonizes Wnt activity. While the WIF1 gene is characterized as a target for epigenetic silencing in some tumor types, WIF1 expression has not been examined in human cervical tissue and cervical cancer. Here, we show that WIF1 is unmethylated and its gene product is expressed in normal cervical epithelium and some cultured cervical tumor lines. In contrast, several cervical cancer lines contained dense CpG methylation within the WIF1 gene, and expression of both WIF1 transcript and protein was restored by culturing cells in the presence of the global DNA demethylating agent 5-aza-2#-deoxycytidine. Using single-molecule MAPit methylation footprinting, we observed differences in chromatin structure within the WIF1 promoter region between cell lines that express and those that do not express WIF1, consistent with transcriptional activity and repression, respectively. The WIF1 promoter was aberrantly methylated in $60% (10 of 17) high-grade highly undifferentiated squamous cell cervical tumors examined, whereas paired normal tissue showed significantly lower levels of CpG methylation. WIF1 protein was not detectable by immunohistochemistry in tumors with quantitatively high levels of WIF1 methylation. Of note, WIF1 protein was not detectable in two of the seven unmethylated cervical tumors examined, suggesting other mechanisms may contribute WIF1 repression. Our findings establish the WIF1 gene as a frequent target for epigenetic silencing in squamous cell carcinoma of the cervix. Background

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“…An increase in MF would not have been surprising based on previous reports indicating that GE is genotoxic in human lymphoblastoid cells [Morris et al, 1998], in the in vitro mouse lymphoma mutation assay, and marginally positive in the in vivo micronucleus test in male but not female mice [Misra et al, 2002]. It is believed that the mutagenic activity of GE is associated with its ability to inhibit topoisomerase enzyme activity leading to DNA strand breaks [Morris et al, 1998].…”

Section: Discussionmentioning

confidence: 97%

“…The isoflavones, genistein (GE) and daidzein (DZ), are found in high concentrations in legumes such as soy, and many studies suggest that consuming diets that are high in soy isolfavones are beneficial for women's hormonal regulation, especially after menopause, offer nutritional support to maintain healthy bones, and support healthy cardiovascular function [Knight and Eden, 1996]. While some of these effects are beneficial, it is likely that these cellular processes are also associated with undesirable side effects that can induce genetic damage [Rao et al, 1997;Morris et al, 1998;Misra et al, 2002].…”

Section: Introductionmentioning

confidence: 99%

17 ?-estradiol and not genistein modulateslacI mutant frequency and types of mutation induced in the heart of ovariectomized big blue rats treated with 7, 12-dimethylbenz[a]anthracene

Manjanatha

Shelton

Rhodes

et al. 2005

Environ. Mol. Mutagen.

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In industrialized countries, heart disease rates are higher among women after menopause. Recent studies indicate that consumption of phytoestorogens, e.g., isoflavones such as genistein (GE), may have potential cardiovascular health benefits; however, no studies have evaluated the effect of these agents on toxicant-induced damage in the heart. Since estrogen receptors are found in the heart, and GE mimics estrogenic effects, we have examined whether or not dietary GE or 17 beta-estradiol (E2) modulates the lacI mutant frequency (MF) in the heart of ovariectomized (OVX) Big Blue rats exposed to the model carcinogen 7,12-dimethylbenz[a]anthracene (DMBA). Groups of female rats were administered 80 mg/kg DMBA or vehicle by gavage and were chronically fed with diets containing 0, 250, or 1,000 microg/g GE or 5 microg/g E2. Sixteen weeks after carcinogen treatment, the animals were sacrificed and the hearts were removed and processed for determining the frequency and types of mutations in the heart tissue. GE and E2 supplementation alone resulted in nonsignificant increases in MF. The DMBA-induced lacI MF in the heart was sevenfold higher than the control (119.8 +/- 18.7 x 10(-6) vs. 17.4 +/- 3.2 x 10(-6); P < 0.001). GE in the diet had no significant effect on DMBA mutagenicity, while feeding E2 to DMBA-treated rats caused a significant reduction in the MF (119.8+/- 18.7 x 10(-6) vs. 61.4 +/- 13.5 x 10(-6); P < 0.017). DNA sequence analysis revealed that the majority of DMBA-induced mutations in rats fed control diet were A:T-->T:A (42%) and G:C-->T:A (19%) transversions, followed by G:C-->A:T (13%) and A:T-->G:C (8%) transitions. Feeding E2 altered the DMBA-induced mutational spectra by decreasing A:T-->T:A (23%) and G:C-->T:A (13%) transversions and increasing G:C-->A:T (24%) and A:T-->G:C (21%) transitions. Taken together, the results suggest that DMBA can induce gene mutations in heart tissue of OVX rats, and while dietary GE had little or no effect on DMBA-induced mutation, dietary E2 reduced the mutagenicity of DMBA.

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p53, mutations, and apoptosis in genistein-exposed human lymphoblastoid cells

Cited by 53 publications

References 60 publications

Growth and cell cycle regulation by isoflavones in human breast carcinoma cells

Growth and cell cycle regulation by isoflavones in human breast carcinoma cells

WIF1 is a frequent target for epigenetic silencing in squamous cell carcinoma of the cervix

17 ?-estradiol and not genistein modulateslacI mutant frequency and types of mutation induced in the heart of ovariectomized big blue rats treated with 7, 12-dimethylbenz[a]anthracene

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