Nutritional supplements in combination with chemotherapy or targeted therapy reduces tumor progression in mice bearing triple-negative breast cancer |
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| Institution: | 1. Department of Human Health and Nutritional Sciences, University of Guelph, Guelph ON, Canada, N1G 2W1;2. Department of Biochemistry, McGill University, Rosalind and Morris Goodman Cancer Research, Montreal, QC, Canada;3. School of Nutrition Sciences, University of Ottawa, Ottawa ON, Canada, K1H 8L1;1. Faculty of Medicine, Mahasarakham University, Maha Sarakham, Thailand;2. Department of Physiology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand;3. Cardiovascular Research Group, Khon Kaen University, Khon Kaen, Thailand;1. Institute of Biomedical Nutrition, Hung-Kuang University, Taichung, 433, Taiwan;2. Department of Medical Research, China Medical University Hospital, Taichung, 404, Taiwan;3. Department of Health and Nutrition Biotechnology, Asia University, Taichung, 413, Taiwan;4. Taiwan Nutraceutical Association, Taipei 115, Taiwan;5. Department of Nursing, Hung-Kuang University, Taichung, 404, Taiwan;6. School of Nursing, China Medical University, Taichung, 404, Taiwan;7. College of Life Sciences, National Chung Hsing University, Taichung, 402, Taiwan;8. College of Engineering, National Chiao Tung University, Hsinchu, 300, Taiwan |
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| Abstract: | The potential anti-cancer properties of selenium (Se) and eicosapentaenoic acid (EPA)/docosahexaenoic acid (DHA) have been documented. However, few studies have been conducted examining anti-tumor effects of nutritional supplements (NS) containing Se and EPA/DHA in combination with anti-cancer agents, such as taxol (Tax), adriamycin (Adr), and avastin (Ava). Compared with triple-negative breast cancer (TNBC)-bearing positive control (TB) mice, a low dose of Tax, Adr, and Ava decreased tumor size and the incidence of metastasis in TB-Tax, TB-Adr, and TB-Ava groups. Combination treatment with anti-cancer agent and NS (2.7 μg Se and 5.1 mg EPA/3.7 mg DHA/g) induced additional decreases in TB-Tax-NS, TB-Adr-NS, and TB-Ava-NS groups. Th1-associated cytokines were increased, and Th2-type cytokines were decreased significantly in TB mice with combination treatment than that of anti-cancer agent treatment alone. Combination treatment with anti-cancer agents and NS has also been shown to further increased tumor malondialdehyde (MDA) levels, lowered hypoxia-inducible factor (HIF)-1α, angiogenic markers (vascular endothelial growth factor VEGF] and CD31) and metastatic potential, as well as reduced heat shock proteins, receptor tyrosine kinase AXL, and surface markers of cancer stem cells, and increased apoptotic proteins. For immune checkpoint molecules, combination treatment was associated with a greater decrease in programmed cell death ligand-1 (PD-L1) in both tumors and mammary glands, but PD-1 level in primary tumors was increased. Our results suggest that combination treatment with low-dose anti-cancer agents (Tax, Adr, and Ava) and oral supplementation of Se/ EPA/DHA significantly decreased tumor growth and metastatic progression in TNBC mice through multiple anti-tumor mechanisms. |
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