A New Role for Lactate in Breast Cancer

Abstract

Lactate dehydrogenase (LDH) is an enzyme that plays a key role in cellular metabolism by converting pyruvate to lactate during anaerobic glycolysis. LDH has been implicated in various cancer types, including breast cancer, where increased LDH activity is associated with tumor growth, invasion, and resistance to therapy. LDH inhibitors are being investigated as potential therapeutic agents in cancer treatment, including breast cancer. Khajah and colleagues investigated the role of LDH inhibitors in both estrogen receptor (ER)⁺ and ER^‑ breast cancer cell lines and in normal breast epithelial cells. A significant reduction in extracellular lactate level, cell proliferation, motility, and invasion was observed after treatment with LDH inhibitors. Subsequently, changes in the levels of vimentin, E‑cadherin, p38 MAPK, ERK1/2, and AKT were also observed. Cancer cell proliferation was preferentially blocked compared with normal epithelial cell inhibition by LDH inhibitors such as quercetin and lonidamine. These results further highlight the role of lactate in breast cancer progression and indicate the practical use of various commercially available LDH inhibitors as promising therapeutic agents to oppose the processes leading to cancer progression. While LDH inhibitors show promise, challenges include achieving selectivity for cancer cells and minimizing toxicity to normal tissues. The development of specific LDH inhibitors with favorable pharmacokinetic properties is an ongoing area of research. Mol Med Rep. 2024 Jan;29(1):12. doi: 10.3892/mmr.2023.1313.