scholarly journals Sulforaphane Diminishes the Formation of Mammary Tumors in Rats Exposed to 17β-Estradiol

Nutrients ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2282
Author(s):  
Dushani L. Palliyaguru ◽  
Li Yang ◽  
Dionysios V. Chartoumpekis ◽  
Stacy G. Wendell ◽  
Marco Fazzari ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Dna Damage ◽  
Mammary Tumor ◽  
Acid Metabolism ◽  
Slow Release ◽  
Mammary Tumorigenesis ◽  
Mammary Glands ◽  
Tumor Formation ◽  
Serum Free Fatty Acids ◽  
17Β Estradiol

Elevated levels of estrogen are a risk factor for breast cancer. In addition to inducing DNA damage, estrogens can enhance cell proliferation as well as modulate fatty acid metabolism that collectively contributes to mammary tumorigenesis. Sulforaphane (SFN) is an isothiocyanate derived from broccoli that is currently under evaluation in multiple clinical trials for prevention of several diseases, including cancer. Previous studies showed that SFN suppressed DNA damage and lipogenesis pathways. Therefore, we hypothesized that administering SFN to animals that are co-exposed to 17β-estradiol (E2) would prevent mammary tumor formation. In our study, 4–6 week old female August Copenhagen Irish rats were implanted with slow-release E2 pellets (3 mg x 3 times) and gavaged 3x/week with either vehicle or 100 μmol/kg SFN for 56 weeks. SFN-treated rats were protected significantly against mammary tumor formation compared to vehicle controls. Mammary glands of SFN-treated rats showed decreased DNA damage while serum free fatty acids and triglyceride species were 1.5 to 2-fold lower in SFN-treated rats. Further characterization also showed that SFN diminished expression of enzymes involved in mammary gland lipogenesis. This study indicated that SFN protects against breast cancer development through multiple potential mechanisms in a clinically relevant hormonal carcinogenesis model.

scholarly journals Methyl-CpG binding domain protein 2 plays a causal role in breast cancer growth and metastasis

2020 ◽  
Author(s):  
Niaz Mahmood ◽  
Ani Arakelian ◽  
Moshe Szyf ◽  
Shafaat A. Rabbani
Keyword(s):  
Breast Cancer ◽  
Dna Methylation ◽  
Mammary Tumor ◽  
Tumor Burden ◽  
Tumor Formation ◽  
Binding Domain ◽  
Causal Role ◽  
Molecular Signaling ◽  
Primary Tumors ◽  
Domain Protein

AbstractMethyl-CpG-binding domain protein 2 (Mbd2), a reader of DNA-methylation, has been implicated in the progression of several types of malignancies, including breast cancer. To test whether Mbd2, which is overexpressed in human breast cancer samples and in MMTV-PyMT mammary pads, plays a causal role in mammary tumor growth and metastasis we depleted Mbd2 in transgenic MMTV-PyMT model of breast cancer by cross-breeding with Mbd2 knockout mice to generate heterozygous (PyMT;Mbd2+/-) and homozygous (PyMT;Mbd2-/-) animals. We found that Mbd2 depletion caused a gene dose-dependent delay in mammary tumor formation, reduced primary tumor burden, and lung metastasis at the experimental endpoint. In addition, animals from the PyMT;Mbd2-/- group survived significantly longer compared to the wildtype (PyMT;Mbd2+/+) and PyMT;Mbd2+/- arms. Transcriptomic and proteomic analyses of the primary tumors obtained from PyMT;Mbd2+/+ and PyMT;Mbd2+/- groups revealed that Mbd2 depletion alters several key determinants of the molecular signaling networks related to tumorigenesis and metastasis, which thereby demonstrate that Mbd2 is regulating transcriptional programs critical for breast cancer. To our knowledge, this is the first study demonstrating a causal role for a DNA-methylation reader in breast cancer. Results from this study will provide the rationale for further development of first-in-class targeted epigenetic therapies against Mbd2 to inhibit the progression of breast and other common cancers.

scholarly journals Ron Receptor Signaling Augments Mammary Tumor Formation and Metastasis in a Murine Model of Breast Cancer

2005 ◽  
Vol 65 (4) ◽  
pp. 1285-1293 ◽  
Author(s):  
Belinda E. Peace ◽  
Kenya Toney-Earley ◽  
Margaret H. Collins ◽  
Susan E. Waltz
Keyword(s):  
Breast Cancer ◽  
Mammary Tumor ◽  
Murine Model ◽  
Tumor Formation ◽  
Receptor Signaling ◽  
Ron Receptor

scholarly journals Tumoral Vitamin D Synthesis by CYP27B1 1-α-Hydroxylase Delays Mammary Tumor Progression in the PyMT-MMTV Mouse Model and Its Action Involves NF-κB Modulation

Endocrinology ◽  
2016 ◽  
Vol 157 (6) ◽  
pp. 2204-2216 ◽  
Author(s):  
Jiarong Li ◽  
Aimée-Lee Luco ◽  
Benoît Ochietti ◽  
Ibtihal Fadhil ◽  
Anne Camirand ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Vitamin D ◽  
Mammary Tumor ◽  
Nuclear Translocation ◽  
Mammary Tumorigenesis ◽  
Mammary Epithelium ◽  
T Antigen ◽  
Biologically Active

Biologically active vitamin D (1,25-dihydroxycholecalciferol or 1,25(OH)2D) is synthetized from inactive prohormone 25-hydroxycholecalciferol (25(OH)D) by the enzyme CYP27B1 1-α-hydroxylase in kidney and several extrarenal tissues including breast. Although the development of breast cancer has been linked to inadequate vitamin D status, the importance of bioactive vitamin D production within tumors themselves is not fully understood. To investigate the role of tumoral vitamin D production in mammary epithelial cell progression to breast cancer, we conducted a Cre-loxP-mediated Cyp27b1 gene ablation in the mammary epithelium of the polyoma middle T antigen-mouse mammary tumor virus (PyMT-MMTV) mouse breast cancer model. Targeted ablation of Cyp27b1 was accompanied by significant acceleration in initiation of spontaneous mammary tumorigenesis. In vivo, cell proliferation, angiogenesis, cell cycle progression, and survival markers were up-regulated in tumors by Cyp27b1 ablation, and apoptosis was decreased. AK thymoma (AKT) phosphorylation and expression of several components of nuclear factor κB (NF-κB), integrin, and signal transducer and activator of transcription 3 (STAT3) signaling pathways were increased in Cyp27b1-ablated tumors compared with nonablated controls. In vitro, 1,25(OH)2D treatment induced a strong antiproliferative action on tumor cells from both ablated and nonablated mice, accompanied by rapid disappearance of NF-κB p65 from the nucleus and segregation in the cytoplasm. In contrast, treatment with the metabolic precursor 25(OH)D was only effective against cells from nonablated mice. 25(OH)D did not inhibit growth of Cyp27b1-ablated cells, and their nuclear NF-κB p65 remained abundant. Our findings demonstrate that in-tumor CYP27B1 1-α-hydroxylase activity plays a crucial role in controlling early oncogene-mediated mammary carcinogenesis events, at least in part by modulating tumoral cell NF-κB p65 nuclear translocation.

scholarly journals Effects of ethanol extract of curry leaves (Murraya koenigii) on HER2 and caspase-3 expression in rat model mammary carcinoma

2021 ◽  
pp. 1988-1994
Author(s):  
Siti Aisyah ◽  
Ekowati Handharyani ◽  
Nurliani Bermawie ◽  
Agus Setiyono
Keyword(s):  
Tumor Cells ◽  
Mammary Tumor ◽  
Leaf Extract ◽  
Caspase 3 ◽  
Tumor Therapy ◽  
Mammary Glands ◽  
Tumor Formation ◽  
Sprague Dawley ◽  
Murraya Koenigii ◽  
Curry Leaves

Background and Aim: Human epidermal growth factor receptor 2 (HER2/erbB2/neu) is a prognostic factor and biomarker for detecting mammary tumor malignancy. Leaves of curry (Murraya koenigii) contain alkaloid, flavonoid, and phenolic compounds that can be cytotoxic to tumor cells. Caspase-3 is an indicator of apoptosis in tumor cells. This study aimed to evaluate the effect of curry leaf extract on the expression of HER2 and caspase-3 in mammary tumor through immunohistochemical analyses. Materials and Methods: Thirty five Sprague-Dawley rats were divided into seven groups: negative control of tumor (P1), positive control of tumor (P2), tumor therapy with methotrexate (P3), and curry leaf extract doses of 300 and 400 mg/ kg body weight/BW after tumor formation (P4, P5), and before tumor formation (P6, P7). Thirty rats of six groups were injected subcutaneously into the mammary glands with 7,12-dimethylbenz(α)-anthracene DMBA) twice within 2 weeks for mammary tumor formation. At the end of the treatments, the rats were euthanized, and their mammary glands were analyzed histopathologically and immunohistochemically using HER2 and caspase-3 antibodies. Results: Regarding the expression of HER2 detected in the epithelial cell membrane of the mammary gland, P2, P3, P4, and P5 revealed positive expression, P6 and P7 showed equivocal expression, while P1 showed negative expression. Regarding caspase-3 expression in the cytoplasm of epithelial cells, it was low in P1, moderate in P2, P5, P6, and P7, and high in P3 and P4. These findings suggest that DMBA injection produced mammary tumors with HER2 as a biomarker of mammary tumor, and high caspase-3 expression in P4 was the effect of curry leaves extract. Conclusion: The extract of curry leaves at a dose of 300 mg/kg BW with preventive and curative effects can potentially be used as an anti-tumor agent, which effectively induces the apoptosis of tumor cells.

scholarly journals Palb2 synergizes with Trp53 to suppress mammary tumor formation in a model of inherited breast cancer

2013 ◽  
Vol 110 (21) ◽  
pp. 8632-8637 ◽  
Author(s):  
C. Bowman-Colin ◽  
B. Xia ◽  
S. Bunting ◽  
C. Klijn ◽  
R. Drost ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Mammary Tumor ◽  
Tumor Formation ◽  
Inherited Breast Cancer

scholarly journals Cumin Prevents 17β-Estradiol-Associated Breast Cancer in ACI Rats

2021 ◽  
Vol 22 (12) ◽  
pp. 6194
Author(s):  
Farrukh Aqil ◽  
Jeyaprakash Jeyabalan ◽  
Radha Munagala ◽  
Iqbal Ahmad ◽  
David J. Schultz ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Volume ◽  
Mammary Tumorigenesis ◽  
Ethanolic Extract ◽  
Developed Countries ◽  
Control Group ◽  
Significant Reversal ◽  
Effective Manner ◽  
17Β Estradiol ◽  
The U.S

Breast cancer (BC) is a leading cause of cancer deaths in women in less developed countries and the second leading cause of cancer death in women in the U.S. In this study, we report the inhibition of E2-mediated mammary tumorigenesis by Cuminum cyminum (cumin) administered via the diet as cumin powder, as well as dried ethanolic extract. Groups of female ACI rats were given either an AIN-93M diet or a diet supplemented with cumin powder (5% and 7.5%, w/w) or dried ethanolic cumin extract (1%, w/w), and then challenged with subcutaneous E2 silastic implants (1.2 cm; 9 mg). The first appearance of a palpable mammary tumor was significantly delayed by both the cumin powder and extract. At the end of the study, the tumor incidence was 96% in the control group, whereas only 55% and 45% animals had palpable tumors in the cumin powder and extract groups, respectively. Significant reductions in tumor volume (660 ± 122 vs. 138 ± 49 and 75 ± 46 mm3) and tumor multiplicity (4.21 ± 0.43 vs. 1.16 ± 0.26 and 0.9 ± 0.29 tumors/animal) were also observed by the cumin powder and cumin extract groups, respectively. The cumin powder diet intervention dose- and time-dependently offset E2-related pituitary growth, and reduced the levels of circulating prolactin and the levels of PCNA in the mammary tissues. Mechanistically, the cumin powder diet resulted in a significant reversal of E2-associated modulation in ERα, CYP1A1 and CYP1B1. Further, the cumin powder diet reversed the expression levels of miRNAs (miR-182, miR-375, miR-127 and miR-206) that were highly modulated by E2 treatment. We analyzed the composition of the extract by GC/MS and established cymene and cuminaldehyde as major components, and further detected no signs of gross or systemic toxicity. Thus, cumin bioactives can significantly delay and prevent E2-mediated mammary tumorigenesis in a safe and effective manner, and warrant continued efforts to develop these clinically translatable spice bioactives as chemopreventives and therapeutics against BC.

Sign in / Sign up

Export Citation Format

Share Document