Unveiling the anticancer potential of plumbagin: targeting pyruvate kinase M2 to induce oxidative stress and apoptosis in hepatoma cells.

Pyruvate kinase M2 (PKM2), a crucial enzyme in the glycolysis pathway, is commonly documented as being overexpressed in cancer cells. Inhibiting PKM2, a strategy to mitigate cancer cell-dependent glycolysis, has demonstrated efficacy in anticancer treatment. In this study, plumbagin, which was originally extracted from the plant L., was discovered as a novel PKM2 inhibitor and it could bind to PKM2 to inhibit the enzymatic activity. Treatment with plumbagin in HepG2 cells resulted in the decrease of PKM2 expression, which in turn reduced the protein kinase function. The mRNA levels of its downstream genes, such as and , were suppressed. Additionally, plumbagin downregulated the expression of intracellular antioxidant proteins, which induced oxidative stress and mitochondrial damage, ultimately triggering apoptosis. Moreover, plumbagin also reduced the migration and proliferation of HepG2 cells. This study offered valuable insights into the molecular mechanism of plumbagin and advocated for the exploration of PKM2 inhibitors as viable possibilities for anticancer therapeutics.