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• W4380787162 abstract "The Warburg effect is prevalent in human cancer. Oridonin (ORI) has excellent anticancer effects, but its exact anticancer mechanism is still unclear.CCK8, EdU, and flow cytometry assay were performed to detect the effect of ORI on cell viability, proliferation and apoptosis, respectively. RNA-seq was carried out to search the underlying mechanisms. Total PKM2, dimeric PKM2, nuclear PKM2 was detected by Western blot. The epidermal growth factor receptor/extracellular signal regulated kinase (EGFR/ERK) signaling was assayed. The binding ability of Importin-α5 to PKM2 was performed by Co-IP experiments. The effect of ORI combined with cysteine (Cys) or fructose-1, 6-diphosphate (FDP) on cancer cells was detected. Mouse xenograft model was established to confirm the molecular mechanisms in vivo.ORI inhibited viability, proliferation and promoted apoptosis of CRC cells. RNA-seq revealed ORI attenuated the Warburg effect in cancer cells. ORI reduced dimeric PKM2 and prevented it from entering the nucleus. ORI did not affect the EGFR/ERK signaling, but reduced Importin-α5 binding to the PKM2 dimer. Cys or FDP reversed or enhanced the effect of ORI. Animal model assay confirmed the molecular mechanisms in vivo.Our study first shows that ORI could have anticancer activity by inhibiting the Warburg effect as a novel activator of PKM2." @default.
• W4380787162 created "2023-06-16" @default.
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• W4380787162 date "2023-09-01" @default.
• W4380787162 modified "2023-09-26" @default.
• W4380787162 title "Oridonin inhibits the occurrence and development of colorectal cancer by reversing the Warburg effect via reducing PKM2 dimer formation and preventing its entry into the nucleus" @default.
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• W4380787162 doi "https://doi.org/10.1016/j.ejphar.2023.175856" @default.
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