Effect of annatto-tocotrienols supplementation on the Development of Mammary Tumors in HER-2/neu Transgenic Mice

Pierpaoli, Elisa; Viola, Valentina; Barucca, Alessandra; Orlando, Federica; Galli, Francesco; Provinciali, Mauro

doi:10.1016/j.freeradbiomed.2012.08.518

Cited by 12 publications

(16 citation statements)

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“…Results shown are representative of two independent experiments. may be induced both by the lowered transcriptional expression of HER-2/neu gene or by the inhibition of p185 HER-2 protein expression and/or function [25][26][27]37]. In agreement with previous findings [32], we confirmed the ability of BBR to reduce HER-2/neu expression and phosphorylation in SK-BR-3 cells.…”

Section: Figsupporting

confidence: 91%

“…The anticancer effect of natural substances was demonstrated not only in vitro but also in animal models, as, for example, the effectiveness of resveratrol, silybin, and annatto-tocotrienols in preventing the development of mammary tumors appearing spontaneously in HER-2/neu transgenic mice [25][26][27]. Furthermore, the effect of natural substances, such as silybin or c-and d-tocotrienols, the more effective natural Vitamin E compounds, on tumor cell growth was related to the induction of apoptosis as well as cellular senescence in human and mouse breast cancer cells [26,27]. Berberine is a phytochemical which has been reported to possess anticancer activity, on the basis of its in vitro effects on tumor cells and of in vivo experimental models of rodents [28].…”

Section: Discussionmentioning

confidence: 99%

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Antitumor effect of novel berberine derivatives in breast cancer cells

Pierpaoli

Arcamone²,

Buzzetti³

et al. 2013

BioFactors

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Breast cancer is the most common malignancy and the most common cause of cancer death in elderly women. Chemoprevention with dietary compounds and their synthetic analogs has emerged as an attractive strategy to prevent carcinogenic progression to invasive cancer. In this study, we investigated the efficacy of some new synthetic derivatives of berberine, a phytochemical isolated from Barberry and other plants, to induce growth arrest of HER-2/neu overexpressing SK-BR-3 breast cancer cells. Supplementation with berberine or with the synthetic derivatives NAX012, NAX013, NAX014, and NAX035 exerted a dose- and time-dependent inhibition of SK-BR-3 cell viability, with a greater effectiveness of NAX012 and NAX014 compounds with respect to berberine. This cytotoxic effect was related to an increased number of apoptotic cells that reached 71.6% and 68.4% after 72 h treatment with 50 µM of NAX012 and NAX014, respectively, compared with 44.2% of berberine. Real-time PCR analyses showed that berberine, NAX012 and NAX014 compounds increased the expression of some cell-cycle checkpoint molecules involved in cell senescence such as p53, p21(WAF1) , p16(INK4a) , and PAI-1, already after 24 h of 50 µM treatments. Furthermore, berberine, NAX012 and NAX014, all reduced both HER-2/neu expression and phosphorylation on tumor cells, the NAX014 compound showing the higher effectiveness. These results provide novel information on the mechanisms involved in the anticancer effects of berberine and demonstrate the greater effectiveness of NAX012 and NAX014 analogs in inducing apoptosis and cellular senescence in HER-2/neu overexpressing tumor cell lines.

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Section: Figsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Antitumor effect of novel berberine derivatives in breast cancer cells

Pierpaoli

Arcamone²,

Buzzetti³

et al. 2013

BioFactors

View full text Add to dashboard Cite

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“…Animals FVB/N wild type and FVB/N HER-2/neu transgenic female mice for the activated rat neu oncogene were originally obtained from Charles River (Hollister, CA) by the Italian National Research Center for Aging (Pierpaoli et al 2013) were housed and breed in the Department of Carcinogenesis and Oncogerontology, N.N. Petrov Research Institute of Oncology.…”

Section: Methodsmentioning

confidence: 99%

Biomarkers of aging, life span and spontaneous carcinogenesis in the wild type and HER-2 transgenic FVB/N female mice

et al. 2015

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FVB/N wild type and transgenic HER-2/neu FVB/N female mice breed at N.N. Petrov Research Institute of Oncology were under observation until natural death without any special treatment. Age-related dynamics of body weight, food consumption and parameters of carbohydrate and lipid metabolism, level of nitric oxide, malonic dialdehyde, catalase, Cu, Zn-superoxide dismutase, vascular endothelial growth factor were studied in both mice strains. The parameters of life span and tumor pathology were studied as well. Cancer-prone transgenic HER-2/neu mice developed in 100 % multiple mammary adenocarcinomas and died before the age of 1 year. Forty tree percent of long-lived wild type mice survived the age of 2 years and 19 %-800 days. The total tumor incidence in wild type mice was 34 %. The age-associated changes in the level of serum IGF-1, glucose and insulin started much earlier in transgene HER-2/neu mice as compared with wild type FVB/N mice. It was suggested that transgenic HER-2/neu involves in initiation of malignization of mammary epithelial cells but also in acceleration of age-related hormonal and metabolic changes in turn promoting mammary carcinogenesis.

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“…γTE-rich tocotrienols dose-dependently decreased tumor growth and enhanced caspase 3 and pro-apoptotic BAD in the TRAMP mice (120). In addition, δTE, which are rich in annatto, dose-dependently reduced tumor size and induced apoptosis and cell senescence in mammary glands in the FVB/N HER-2/neu transgenic mice (121).…”

Section: In Vivo Anti-proliferation and Pro-apoptotic Activity Of Vitmentioning

confidence: 98%

Natural forms of vitamin E and metabolites—regulation of cancer cell death and underlying mechanisms

Jiang

2018

IUBMB Life

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The disappointing results from large clinical studies of α‐tocopherol (αT), the major form of vitamin E in tissues, for prevention of chronic diseases including cancer have cast doubt on not only αT but also other forms of vitamin E regarding their role in preventing carcinogenesis. However, basic research has shown that specific forms of vitamin E such as γ‐tocopherol (γT), δ‐tocopherol (δT), γ‐tocotrienol (γTE) and δ‐tocotrienol (δTE) can inhibit the growth and induce death of many types of cancer cells, and are capable of suppressing cancer development in preclinical cancer models. For these activities, these vitamin E forms are much stronger than αT. Further, recent research revealed novel anti‐inflammatory and anticancer effects of vitamin E metabolites including 13′‐carboxychromanols. This review focuses on anti‐proliferation and induction of death in cancer cells by vitamin E forms and metabolites, and discuss mechanisms underlying these anticancer activities. The existing in vitro and in vivo evidence indicates that γT, δT, tocotrienols and 13′‐carboxychromanols have anti‐cancer activities via modulating key signaling or mediators that regulate cell death and tumor progression, such as eicosanoids, NF‐κB, STAT3, PI3K, and sphingolipid metabolism. These results provide useful scientific rationales and mechanistic understanding for further translation of basic discoveries to the clinic with respect to potential use of these vitamin E forms and metabolites for cancer prevention and therapy. © 2018 IUBMB Life, 71(4):495–506, 2019

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Effect of annatto-tocotrienols supplementation on the Development of Mammary Tumors in HER-2/neu Transgenic Mice

Cited by 12 publications

References 0 publications

Antitumor effect of novel berberine derivatives in breast cancer cells

Antitumor effect of novel berberine derivatives in breast cancer cells

Biomarkers of aging, life span and spontaneous carcinogenesis in the wild type and HER-2 transgenic FVB/N female mice

Natural forms of vitamin E and metabolites—regulation of cancer cell death and underlying mechanisms

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