Journal of Cancer Research

The Role of NF-κB, Melatonin, and LDH-A in Breast Cancer Initiation, Promotion, and Progression in Rats Exposed to N-Methyl-Nitroso-Urea: Implications for Tumor Metabolic Reprogram

Abstract

Alexandre Tavartkiladze, Gaiane Simonia, Russel J Reiter, Ruite Lou, Nana Okrostsvaridze, Pati Revazishvili, Irine Andronikashvili, Pirdara Nozadze, Givi Tavartkiladze and Malvina Javakhadze

Breast cancer remains a significant focus in oncology due to its complexity and variable progression. This study investigates the initiation, promotion, and progression of breast cancer in 97 rats induced with carcinogenesis by N-methyl-nitroso-urea (NMU). We analyzed stress-responsive hormones, NF-κB pathway activation, melatonin secretion, and lactate dehydrogenase (LDH) dynamics during disease progression. The study revealed that tumor development correlates with the overactivation of the NF-κB pathway and a simultaneous reduction in melatonin levels, evident in both nocturnal and diurnal cycles. Additionally, LDH-A (LDH-5), a key enzyme in glycolysis, was shown to dominate metabolic processes during tumor progression, suggesting metabolic reprogramming. These findings highlight the intricate interplay of stress hormones, inflammation, and metabolism in cancer and the potential for targeting these pathways therapeutically.

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