Nutritional supplements in combination with chemotherapy or targeted therapy reduces tumor progression in mice bearing triple-negative breast cancer

Chih-Hung Guo; Simon Hsia; Chieh-Han Chung; Yi-Chun Lin; Min-Yi Shih; Pei-Chung Chen; Chia-Lin Peng; Susanne M Henning; Guoo-Shyng W Hsu; Zhaoping Li

doi:10.1016/j.jnutbio.2020.108504

Nutritional supplements in combination with chemotherapy or targeted therapy reduces tumor progression in mice bearing triple-negative breast cancer

J Nutr Biochem. 2021 Jan:87:108504. doi: 10.1016/j.jnutbio.2020.108504. Epub 2020 Sep 19.

Authors

Affiliations

¹ Micronutrition and Biomedical Nutrition Lab, Institute of Biomedical Nutrition, Hung-Kuang University, Taichung 433, Taiwan; Taiwan Nutraceutical Association, Taipei 105, Taiwan. Electronic address: eillyguo@sunrise.hk.edu.tw.
² Taiwan Nutraceutical Association, Taipei 105, Taiwan.
³ UCLA Center for Human Nutrition, David Geffen School of Medicine at UCLA, Los Angeles, California 90095, USA.
⁴ Department of Nutritional Science, Fu Jen University, New Taipei City 242, Taiwan.
⁵ UCLA Center for Human Nutrition, David Geffen School of Medicine at UCLA, Los Angeles, California 90095, USA. Electronic address: zli@mednet.ucla.edu.

PMID: 32956826
DOI: 10.1016/j.jnutbio.2020.108504

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.

Keywords: Anti-cancer effect; Chemo- and targeted therapy agents; EPA and DHA; Mice; Selenium; Triple-negative breast cancer.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antineoplastic Agents / therapeutic use*
Cell Line, Tumor
Dietary Supplements* / analysis
Disease Progression
Docosahexaenoic Acids / therapeutic use*
Eicosapentaenoic Acid / therapeutic use*
Female
Mice
Mice, Inbred BALB C
Selenium / therapeutic use*
Triple Negative Breast Neoplasms / pathology
Triple Negative Breast Neoplasms / therapy*

Substances

Antineoplastic Agents
Docosahexaenoic Acids
Eicosapentaenoic Acid
Selenium