Wu Jun, Ding Zhenjiang, Tu Jingwen, Osama Alsiddig, Nie Qiuying, Cai Wenqing, Zhang Baoxin
State Key Laboratory of Applied Organic Chemistry and College of Chemistry and Chemical Engineering, Lanzhou University Lanzhou 730000 China
Beijing Key Laboratory of the Innovative Development of Functional Staple and Nutritional Intervention for Chronic Diseases, China National Research Institute of Food and Fermentation Industries Beijing 100015 China.
RSC Med Chem. 2024 Sep 20;15(12):4126-37. doi: 10.1039/d4md00519h.
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.
丙酮酸激酶M2（PKM2）是糖酵解途径中的一种关键酶，通常被记录为在癌细胞中过表达。抑制PKM2是一种减轻癌细胞依赖糖酵解的策略，已在抗癌治疗中显示出疗效。在本研究中，最初从植物L.中提取的白花丹素被发现是一种新型的PKM2抑制剂，它可以与PKM2结合以抑制酶活性。用白花丹素处理HepG2细胞导致PKM2表达下降，进而降低蛋白激酶功能。其下游基因如和的mRNA水平受到抑制。此外，白花丹素下调细胞内抗氧化蛋白的表达，诱导氧化应激和线粒体损伤，最终引发细胞凋亡。此外，白花丹素还降低了HepG2细胞的迁移和增殖。本研究为白花丹素的分子机制提供了有价值的见解，并提倡探索PKM2抑制剂作为抗癌治疗的可行选择。
