Abstract 5562: BreastDefend enhances the effects of tamoxifen in estrogen receptor-positive human breast cancer in vitro and animal models in vivo
| Autor: | Daniel Sliva, Shujie Cheng, Victor Castillo, Mark Alvarado, Georg Sandusky, Jagadish Loganathan, Isaac Eliaz |
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| Rok vydání: | 2015 |
| Předmět: |
Cancer Research
medicine.medical_specialty business.industry medicine.drug_class Estrogen receptor Cancer medicine.disease medicine.disease_cause Metastasis Endocrinology Oncology Estrogen In vivo Internal medicine Cancer cell medicine Cancer research skin and connective tissue diseases business Carcinogenesis Tamoxifen medicine.drug |
| Zdroj: | Cancer Research. 75:5562-5562 |
| ISSN: | 1538-7445 0008-5472 |
| Popis: | In this study we evaluated the combined effects of the natural product/dietary supplement BreastDefend (BD) and tamoxifen (TAM) on MCF-7 estrogen receptor-positive (ER+) human breast cancer cells in vitro and an orthotopic mouse model in vivo. BD has been studied previously in preclinical models, and shown to exert significant effects on MDA-MB-231 triple-negative breast cancer cells. The proliferation of MCF-7 cells was evaluated using MTT assays, whereas the expression of genes involved in the molecular mechanisms of cancer was evaluated using DNA microarrays. MCF-7 cells were stimulated with estradiol (10 nM) and treated with TAM (1 μM), BD (10 μg/ml), and the combination of TAM and BD for 3 days and 6 days. Compared with control, BD enhanced the anti-proliferative activity of TAM significantly (P < 0.05), and the combination of BD and TAM induced apoptosis. The results of DNA microarray analyses suggested that the pro-apoptotic activity of BD and TAM in MCF-7 cells was associated with the significant upregulation of BRAF (an oncogene that can block proliferation and induce apoptosis) and downregulation of BCL2 (an apoptosis inhibitor) and FN1 (fibronectin, a glycoprotein involved in tumorigenesis and metastasis) expression. In the orthotopic model MCF-7 cells were implanted into the mammary fat pads of female ovariectomized nude mice (n = 12-13). The mice received subcutaneous pellets that released estradiol and TAM, whereas BD was administered orally via intragastric gavage. All groups, including control, received estradiol. The combination of BD and TAM suppressed tumor size in vivo markedly compared with the BD and TAM alone groups. The inhibition of tumor growth was associated with the induction of the cell cycle inhibitor protein p21 in MCF-7-generated breast tumors. In summary, this study suggests that BD could be considered for use in clinical studies as an adjuvant therapy in conjunction with TAM for the treatment of ER+ human breast cancer. Citation Format: Shujie Cheng, Mark Alvarado, Jagadish Loganathan, Victor Castillo, Georg Sandusky, Isaac Eliaz, Daniel Sliva. BreastDefend enhances the effects of tamoxifen in estrogen receptor-positive human breast cancer in vitro and animal models in vivo. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5562. doi:10.1158/1538-7445.AM2015-5562 |
| Databáze: | OpenAIRE |
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