Dietary Flaxseed–Trastuzumab Interactive Effects on the Growth of HER2-Overexpressing Human Breast Tumors (BT-474)
- 26 March 2013
- journal article
- research article
- Published by Taylor & Francis in Nutrition and Cancer
- Vol. 65 (3), 451-459
- https://doi.org/10.1080/01635581.2013.756921
Abstract
Flaxseed (FS) reduces breast tumorigenesis and human epidermal growth factor receptor 2 (HER2) expression in postmenopausal patients and animal models. The primary treatment for HER2-overexpressing tumors is trastuzumab (TRAS). FS oil enhances TRAS effectiveness in athymic mice but the FS effect is unknown and was therefore determined. Athymic mice with established BT-474 tumors were fed the basal diet (control), or 10% FS diet, with or without TRAS (2.5mg/kg) treatment for 5 wk. After 2 wk, TRAS and FS reduced tumor size with a trend for an FS × TRAS interaction; however, after 5 wk, only TRAS reduced tumor size and increased tumor apoptosis. FS did not further improve TRAS effect but increased overall survival. TRAS reduced signaling biomarkers [phosphorylated HER2 and mitogen-activated protein kinase (MAPK) proteins; Akt1, Akt2, MAPK, and estrogen receptor-α mRNA], FS reduced phosphorylated-Akt1 protein, and FS × TRAS interactions were seen for HER2 mRNA and phosphorylated-Akt1 protein. FS, with and without TRAS, increased tumor n-3 PUFA levels and serum lignans indicating potential roles in the observed effect. In conclusion, TRAS reduces tumor growth by influencing HER2 signaling. Dietary FS has minimal tumor-reducing effect, does not interfere with TRAS action, but improves overall survival in athymic mice.Keywords
This publication has 36 references indexed in Scilit:
- Intake of Phytoestrogen Foods and Supplements Among Women Recently Diagnosed With Breast Cancer in Ontario, CanadaNutrition and Cancer, 2012
- Adjuvant Trastuzumab in HER2-Positive Breast CancerNew England Journal of Medicine, 2011
- Prediagnostic plasma enterolactone levels and mortality among women with breast cancerBreast Cancer Research and Treatment, 2011
- Dietary lignan intakes in relation to survival among women with breast cancer: the Western New York Exposures and Breast Cancer (WEB) StudyBreast Cancer Research and Treatment, 2009
- tabAnti-HER2 (erbB-2) oncogene effects of phenolic compounds directly isolated from commercial Extra-Virgin Olive Oil (EVOO)BMC Cancer, 2008
- Modulation of angiogenesis by ω-3 polyunsaturated fatty acids is mediated by cyclooxygenasesBlood, 2008
- Trastuzumab: mechanism of action, resistance and future perspectives in HER2-overexpressing breast cancerAnnals of Oncology, 2007
- Nordihydroguaiaretic Acid (NDGA) Inhibits the IGF-1 and c-erbB2/HER2/neu Receptors and Suppresses Growth in Breast Cancer CellsBreast Cancer Research and Treatment, 2005
- Dietary Flaxseed Alters Tumor Biological Markers in Postmenopausal Breast CancerClinical Cancer Research, 2005
- Mechanism of action of trastuzumab and scientific updateSeminars in Oncology, 2001