Molecular mechanisms underlying the antitumor activity of human and bovine alpha-lactalbumin-oleic acid complexes in a murine mammary adenocarcinoma model.

Abstract

The alpha-lactalbumin-oleic acid complexes (BAMLET and HAMLET) derivatives have shown remarkable anticancer capabilities in various preclinical studies with potential applications in oncology. The current study investigates the anti-cancer activity of synthesized human alpha-lactalbumin oleic acid (HAMLET) and bovine alpha-lactalbumin oleic acid (BAMLET) complexes on AN3 mouse mammary adenocarcinoma cancer cell line, a long-standing model for cancer research. We investigated multiple therapeutic endpoints including tumor volume reduction, survival rates, histopathological changes, as well as the molecular mechanisms allying the treatment response. A significant suppression of tumor growth was observed in both groups treated with HAMLET and BAMLET when compared with the control group, with HAMLET showing slightly better effectiveness in tumor growth inhibition. Histological examination revealed tumor necrosis, apoptosis, and decreased cell proliferation in treated mice, cancer cells were dying and also growth architecture was disrupted which indicates that both complexes cancer cell death. Thus, we investigated major molecular pathways associated with the anticancer activity of these compounds. Findings revealed the activation of supportive apoptotic pathways alongside downregulation of fundamental oncogenes linked to growth endurance and metastasis. Likewise, the safe response was augmented in the treated groups as shown by greater infiltration of immune cells into the tumor microenvironment. Survival rates were significantly higher in the HAMLET and BAMLET treatment groups compared to control, suggesting that these assemblies may prolong survival by effectively reducing cancer burden. The results highlight once again the exceptional breast cancer treatment efficacy of the alpha-lactalbumin-oleic acid complex.