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

• DOI: 10.1016/j.ejphar.2023.175856
• Publication Date: 2023-06-15T13:10:06Z
• Authors: Fan Chen; Junnan Liao; Pinghui Wu; Li Cheng; Yingchao Ma; Linghan Zhang; Xiaomin Leng; Xiuzhi Zhu; Zhiping Liu; Fuhua Xie
• Keywords: PKM2; Warburg Effect

The Warburg effect is prevalent in human cancer. Oridonin (ORI) has excellent anticancer effects, but its exact mechanism still unclear. CCK8, EdU, and flow cytometry assay were performed to detect the of ORI on cell viability, proliferation apoptosis, respectively. RNA-seq was carried out search underlying mechanisms. Total PKM2, dimeric nuclear PKM2 detected by Western blot. epidermal growth factor receptor/extracellular signal regulated kinase (EGFR/ERK) signaling assayed. binding ability Importin-α5 Co-IP experiments. combined with cysteine (Cys) or fructose-1, 6-diphosphate (FDP) cancer cells detected. Mouse xenograft model established confirm molecular mechanisms vivo. inhibited promoted apoptosis CRC cells. revealed attenuated reduced prevented it from entering nucleus. did not affect EGFR/ERK signaling, dimer. Cys FDP reversed enhanced ORI. Animal confirmed Our study first shows that could have activity inhibiting as a novel activator PKM2.