Influence of pH on the Cytotoxic Activity of Organic Acids against Breast Cancer Cells

Abstract Cancer is among the leading causes of death, and breast cancer is the most common cancer in women worldwide. Cancer cells including breast cancer cells generate a reversed pH gradient. Cancer cells have lower extracellular pH (pHe) of ~6.7 - 7.1 and higher intracellular pH (pHi) of 7.4, while normal cells have pHe of 7.4 and lower pHi of 7.2. Exogenous pH changes can modulate the cell growth and cell cycle of breast cancer cells. Here, we investigated how organic acids affected breast cancer cells. MDA-MB-231 cell lines, metastatic human breast cancer cells, were cultured in medium with ten organic acids, and the cytotoxicity of all organic acids against MDA-MB-231 cells was measured. Among ten organic acids, four organic acids, succinic acid (SA), fumaric acid (FA), tartaric acid (TA), and citric acid (CA), were more toxic to MDA-MB-231 cells than other organic acids. The further results demonstrated that the cytotoxicity was caused mainly by acidic pH or pH changes of four organic acids. Four organic acids also affected cell toxicity, cell density, and morphology of MDA-MB-231 spheroids. The information of this research will be beneficial to design novel anticancer drugs to treat breast cancer.