Prepubertal octylphenol exposure up-regulate BRCA1 expression, down-regulate ERα expression and reduce rat mammary tumorigenesis

Peng, Junhua; Zhang, Feng; Zhang, Hua-Xing; Fan, Huiying

doi:10.1016/j.canep.2009.04.017

Cited by 11 publications

(4 citation statements)

References 40 publications

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“…This model is quite different from MMTV-erbB2 Tg mice used by Jenkins et al ( 32 ) or the carcinogen DMBA (dimethylbenz[a]anthracene) induced tumorigenesis described by Betancourt et al ( 33 ) in which both teams demonstrated a pro-tumoral effect of BPA exposure. Opposite results were obtained by Peng et al ( 34 ), who reported a protective effect of a 40 mg/kg octylphenol exposure in DMBA-treated Sprague–Dawley rats. Nevertheless, these data suggest that a transient direct exposure to alkyphenols at adulthood is not sufficient by itself to trigger mammary carcinogenesis.…”

Section: Discussionmentioning

confidence: 61%

Low-Dose Alkylphenol Exposure Promotes Mammary Epithelium Alterations and Transgenerational Developmental Defects, But Does Not Enhance Tumorigenic Behavior of Breast Cancer Cells

et al. 2017

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Fetal and neonatal exposure to long-chain alkylphenols has been suspected to promote breast developmental disorders and consequently to increase breast cancer risk. However, disease predisposition from developmental exposures remains unclear. In this work, human MCF-10A mammary epithelial cells were exposed in vitro to a low dose of a realistic (4-nonylphenol + 4-tert-octylphenol) mixture. Transcriptome and cell-phenotype analyses combined to functional and signaling network modeling indicated that long-chain alkylphenols triggered enhanced proliferation, migration ability, and apoptosis resistance and shed light on the underlying molecular mechanisms which involved the human estrogen receptor alpha 36 (ERα36) variant. A male mouse-inherited transgenerational model of exposure to three environmentally relevant doses of the alkylphenol mix was set up in order to determine whether and how it would impact on mammary gland architecture. Mammary glands from F3 progeny obtained after intrabuccal chronic exposure of C57BL/6J P0 pregnant mice followed by F1–F3 male inheritance displayed an altered histology which correlated with the phenotypes observed in vitro in human mammary epithelial cells. Since cellular phenotypes are similar in vivo and in vitro and involve the unique ERα36 human variant, such consequences of alkylphenol exposure could be extrapolated from mouse model to human. However, transient alkylphenol treatments combined to ERα36 overexpression in mammary epithelial cells were not sufficient to trigger tumorigenesis in xenografted Nude mice. Therefore, it remains to be determined if low-dose alkylphenol transgenerational exposure and subsequent abnormal mammary gland development could account for an increased breast cancer susceptibility.

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Section: Discussionmentioning

confidence: 61%

Low-Dose Alkylphenol Exposure Promotes Mammary Epithelium Alterations and Transgenerational Developmental Defects, But Does Not Enhance Tumorigenic Behavior of Breast Cancer Cells

et al. 2017

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“…Hwang et al (29) reported that genistein in combination with capsaicin exerts antiinflammatory and anticarcinogenic properties through the modulation of MAPK and COX-2 and possibly various mitogen-activated protein kinases synergistically or nonsynergistically. Peng et al (30) reported that prepubertal exposure to 500 mg/kg genistein and 40 mg/kg octylphenol reduced the susceptibility to develop carcinogen-induced mammary tumors in female Sprague-Dawley rats. The used concentration of genistein and octylphenol is higher compared with other studies; these findings show a reduction in carcinogeninduced mammary tumorigenesis in rats with different concentrations and are in line with the previous observations.…”

Section: Discussionmentioning

confidence: 97%

Inhibitory Effects of Combination of Lycopene and Genistein on 7,12- Dimethyl Benz(a)anthracene-Induced Breast Cancer in Rats

Şahin¹,

Tuzcu²,

Şahin³

et al. 2011

Nutrition and Cancer

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Breast cancer is one of the most common cancers in women. Carotenoids and soy isoflavones have been postulated to have breast cancer preventive effects. We investigated the potential preventive effects of lycopene and genistein, alone and in combination, on breast cancer development in female Wistar rats treated with 7,12-dimethylbenz[a]anthracene (DMBA), a carcinogen known to induce breast tumors. Mammary carcinogenesis was initiated by a single, oral gavage of DMBA (80 mg/kg body weight) at 55 days of animal age. Fifty female Wistar rats were divided into 5 experimental groups having 10 animals per group: Group 1 (normal control), Group 2 (DMBA control), Group 3 (DMBA + lycopene), Group 4 (DMBA + genistein), and Group 5 (DMBA + lycopene and genistein). Rats were fed either lycopene (20 mg /kg bw) or genistein (2 mg /kg bw) by oral gavage (3 times per week) starting 2 wk prior to DMBA injection. Treatment was continued for 20 wk. Rats treated with DMBA developed mammary tumors with 100% tumor incidence during the 20-wk study. Inhibition of mammary cancer incidence by lycopene (70%), genistein (60%) and their combination (40%) was observed. Tumor weight decreased by 48%, 61%, and 67%, and mean tumor volume decreased by 18%, 35%, and 65% with lycopene, genistein, and lycopene + genistein, respectively (P < 0.01 for the combination). The proportions of adenocarcinoma masses decreased with lycopene and genistein combination (P < 0.05). Administration of lycopene and genistein combination suppressed breast cancer development and was associated with a decrease in MDA, 8-isoprostane, and 8-OhdG levels and with an increase in serum lycopene and genistein levels. Animals administered DMBA developed breast cancer, which was associated with increased expression of Bcl-2 and decreased expression of Bax, caspase 3, and caspase 9 in mammary tissues. Administration of genistein and lycopene in combination was more effective in inhibiting DMBA-induced breast tumors and modulating the expression of apoptosis associated proteins than the administration of each agent alone. Our results suggest that lycopene and genistein are potent antioxidants and, when given in combination, offer maximum protection against DMBA-induced mammary carcinogenesis.

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“…Briefly, all four epidemiologic studies that have examined this hypothesis found protective effects associated with modest soy intake during childhood and/or adolescence with reductions in risk ranging from 28 to 60 percent [93,94,95,96]. In addition, young rodents exposed to genistein even briefly develop far fewer chemically-induced mammary tumors than control animals [97,98]. The early soy intake hypothesis is consistent with the lack of favorable effects of adult soy exposure on markers of breast cancer risk (see reference for review) [99].…”

Section: Role Of Soy In Reducing Vegetarian Risk Of Chronic Diseasementioning

confidence: 99%

The Role of Soy in Vegetarian Diets

Messina

2010

Nutrients

104

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Soyfoods have long been prized among vegetarians for both their high protein content and versatility. Soybeans differ markedly in macronutrient content from other legumes, being much higher in fat and protein, and lower in carbohydrate. In recent years however, soyfoods and specific soybean constituents, especially isoflavones, have been the subject of an impressive amount of research. Nearly 2,000 soy-related papers are published annually. This research has focused primarily on the benefits that soyfoods may provide independent of their nutrient content. There is particular interest in the role that soyfoods have in reducing risk of heart disease, osteoporosis and certain forms of cancer. However, the estrogen-like effects of isoflavones observed in animal studies have also raised concerns about potential harmful effects of soyfood consumption. This review addresses questions related to soy and chronic disease risk, provides recommendations for optimal intakes, and discusses potential contraindications. As reviewed, the evidence indicates that, with the exception of those individuals allergic to soy protein, soyfoods can play a beneficial role in the diets of vegetarians. Concerns about adverse effects are not supported by the clinical or epidemiologic literature. Based on the soy intake associated with health benefits in the epidemiologic studies and the benefits noted in clinical trials, optimal adult soy intake would appear to be between two and four servings per day.

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Prepubertal octylphenol exposure up-regulate BRCA1 expression, down-regulate ERα expression and reduce rat mammary tumorigenesis

Cited by 11 publications

References 40 publications

Low-Dose Alkylphenol Exposure Promotes Mammary Epithelium Alterations and Transgenerational Developmental Defects, But Does Not Enhance Tumorigenic Behavior of Breast Cancer Cells

Low-Dose Alkylphenol Exposure Promotes Mammary Epithelium Alterations and Transgenerational Developmental Defects, But Does Not Enhance Tumorigenic Behavior of Breast Cancer Cells

Inhibitory Effects of Combination of Lycopene and Genistein on 7,12- Dimethyl Benz(a)anthracene-Induced Breast Cancer in Rats

The Role of Soy in Vegetarian Diets

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