Preliminary exploration of molecular mechanism of the anticancer activity of a novel lead lactate dehydrogenase inhibitor against pancreatic cancer

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer-related death in the United States, with a long-term survival rate of just under 10%. Chemotherapy is one of the standard treatment options for pancreatic cancer; however, the rapid development of resistance to chemotherapeutic agents represents a significant bottleneck. Therefore, identifying new biological drug targets and exploring biomolecular mechanisms that lead to chemoresistance in pancreatic cancer is urgently required. Cancer cells rewire their metabolic pathways to support their growth and proliferation. Unlike normal cells, cancer cells prefer aerobic fermentation, a phenomenon known as the Warburg effect, where they convert glucose to lactic acid even in the presence of oxygen. Warburg effect in cancer cells is regulated by lactate dehydrogenase-A (LDHA) that is overexpressed in many tumor types. Here, we report our preliminary studies on the molecular mechanisms underlying the anticancer activity of a novel LDHA inhibitor, compound 23, in pancreatic cancer cell lines.