Inhibition of vacuolar-type ATPase suppresses breast cancer cell survival

Vacuolar-type ATPases (V-ATPases) couple ATP hydrolysis and proton transport across membranes in eukaryotic cells. This regulation of the protein gradient often plays a role in driving Ca²⁺ gradients, maintaining pH homeostasis, and stimulating HCO3- reabsorption. V-ATPases may also play a role in tumor biology. Hypoxic conditions often occur during the development of solid tumors, leading to acidosis, which can induce DNA damage. To prevent intracellular acidosis and its negative downstream effects, tumor cells may upregulate expression of pH regulators such as V-ATPases as a way to remove protons from tumor cells.

An article recently published in Cancer Research highlights V-ATPases as a potential target to suppress tumor growth. Inhibition of these enzymes triggered metabolic stress by interfering with HIF-1α signaling and iron metabolism. As a result, cell cycle progression halted and apoptosis was induced, preventing growth of breast cancer cells.

The results from this study indicate the potential for V-ATPase inhibition in the treatment of cancers and suggest further research exploration of this mechanism in cellular and animal models.

For more information on the original study, click here.

LKT carries several compounds that alter vacuolar-type ATPase activity! Click the representative links below for more information.

• B0025 Bafilomycin A1
• B0026 Bafilomycin B1
• E5358 Enoxacin
• M0255 Manzamine A

References:

Schneider LS, von Schwarzenberg K, Lehr T, et al. Vacuolar-ATPase Inhibition Blocks Iron Metabolism to Mediate Therapeutic Effects in Breast Cancer. Cancer Res. 2015 Jul 15;75(14):2863-74. PMID: 26018087.

Izumi H, Torigoe T, Ishiguchi H, et al. Cellular pH regulators: potentially promising molecular targets for cancer chemotherapy. Cancer Treat Rev. 2003 Dec;29(6):541-9. PMID: 14585264.