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This article explores the potential of plumbagin as a novel inhibitor of Pyruvate Kinase M2 (PKM2), a key enzyme in cancer cell glycolysis. The study found that plumbagin could bind to PKM2 and reduce its enzymatic activity, leading to decreased expression of PKM2 and its downstream genes, ultimately inducing oxidative stress and apoptosis in hepatoma cells. Plumbagin also demonstrated the ability to inhibit cell migration and proliferation. These findings suggest that PKM2 inhibitors, like plumbagin, could be a promising avenue for developing new anticancer therapeutics.
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 Plumbago zeylanica 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 LDHA and MYC, 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.
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