BAMLET administration via drinking water inhibits intestinal tumor development and promotes long-term health

• Published in: Scientific reports Vol. 14; no. 1; p. 3838
• Main Authors: Tran, Hien Thi, Wan, Murphy Lam Yim, Ambite, Ines, Cavalera, Michele, Grossi, Mario, Háček, Jaromir, Esmaeili, Parisa, Carneiro, António N. B. M., Chaudhuri, Arunima, Ahmadi, Shahram, Svanborg, Catharina
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 15.02.2024; Nature Publishing Group; Nature Portfolio
• Subjects: 631/67/1059; 631/67/1504/1885/1393; Angiogenesis; Antitumor activity; Cancer; Cancer and Oncology; Cancer och onkologi; Carbohydrate metabolism; Clinical Medicine; Colorectal cancer; Colorectal carcinoma; Drinking water; Gene expression; Humanities and Social Sciences; Intestine; Klinisk medicin; Lactalbumin; Lipid metabolism; Lung diseases; Medical and Health Sciences; Medicin och hälsovetenskap; Metabolic response; Metastases; multidisciplinary; PD-1 protein; Science; Science (multidisciplinary); Toxicity; Tumor cells; Tumors; Wnt protein; β-Catenin
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-024-54040-w

Though new targeted therapies for colorectal cancer, which progresses from local intestinal tumors to metastatic disease, are being developed, tumor specificity remains an important problem, and side effects a major concern. Here, we show that the protein-fatty acid complex BAMLET ( b ovine a lpha-lactalbumin m ade le thal to t umor cells) can act as a peroral treatment for colorectal cancer. Apc Min/ + mice, which carry mutations relevant to hereditary and sporadic human colorectal cancer, that received BAMLET in the drinking water showed long-term protection against tumor development and decreased expression of tumor growth-, migration-, metastasis- and angiogenesis-related genes. BAMLET treatment via drinking water inhibited the Wnt/β-catenin and PD-1 signaling pathways and prolonged survival without evidence of toxicity. Systemic disease in the lungs, livers, spleens, and kidneys, which accompanied tumor progression, was inhibited by BAMLET treatment. The metabolic response to BAMLET included carbohydrate and lipid metabolism, which were inhibited in tumor prone Apc Min/ + mice and weakly regulated in C57BL/6 mice, suggesting potential health benefits of peroral BAMLET administration in addition to the potent antitumor effects. Together, these findings suggest that BAMLET administration in the drinking water maintains antitumor pressure by removing emergent cancer cells and reprogramming gene expression in intestinal and extra-intestinal tissues.