Intermittent Fasting Attenuates Obesity-Induced Triple-Negative Breast Cancer Progression by Disrupting Cell Cycle, Epithelial-Mesenchymal Transition, Immune Contexture, and Proinflammatory Signature

• Published in: Nutrients Vol. 16; no. 13; p. 2101
• Main Authors: Son, Deok-Soo, Done, Kaitlyn A, Son, Jubin, Izban, Michael G, Virgous, Carlos, Lee, Eun-Sook, Adunyah, Samuel E
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.07.2024
• Subjects: Animals; Breast cancer; Cell Cycle; Cell growth; Cell Line, Tumor; Cell Movement; Cell Proliferation; Chemotherapy; Cold; Complications and side effects; Disease Progression; Epithelial-Mesenchymal Transition; Fasting; Female; Flow cytometry; Forecasts and trends; Health aspects; Health disparities; Humans; Inflammation; Intermittent Fasting; Mice; Mice, Obese; Minority & ethnic groups; Obesity; Obesity - complications; Penicillin; Phenols; proinflammatory signature; Reducing diets; Triple Negative Breast Neoplasms; triple-negative breast cancer; Tumor Microenvironment; Womens health; United States; United States > US; epithelial–mesenchymal transition; triple-negative breast cancer; intermittent fasting; obesity; proinflammatory signature
• ISSN: 2072-6643; 2072-6643
• DOI: 10.3390/nu16132101

Obesity is associated with one-fifth of cancer deaths, and breast cancer is one of the obesity-related cancers. Triple-negative breast cancer (TNBC) lacks estrogen and progesterone receptors and human epidermal growth factor receptor 2, leading to the absence of these therapeutic targets, followed by poor overall survival. We investigated if obesity could hasten TNBC progression and intermittent fasting (IF) could attenuate the progression of obesity-related TNBC. Our meta-analysis of the TNBC outcomes literature showed that obesity led to poorer overall survival in TNBC patients. Fasting-mimicking media reduced cell proliferation disrupted the cell cycle, and decreased cell migration and invasion. IF decreased body weight in obese mice but no change in normal mice. Obese mice exhibited elevated plasma glucose and cholesterol levels, increased tumor volume and weight, and enhanced macrophage accumulation in tumors. The obesity-exacerbated TNBC progression was attenuated after IF, which decreased cyclin B1 and vimentin levels and reduced the proinflammatory signature in the obesity-associated tumor microenvironment. IF attenuated obesity-induced TNBC progression through reduced obesity and tumor burdens in cell and animal experiments, supporting the potential of a cost-effective adjuvant IF therapy for TNBC through lifestyle change. Further evidence is needed of these IF benefits in TNBC, including from human clinical trials.