Butein suppresses pancreatic cancer progression by downregulating CDK2 and disrupting CDK2/CyclinA2 interaction
- Biochem Pharmacol. 2026 Sep;251(Pt 1):118099. doi: 10.1016/j.bcp.2026.118099.
- 1. School of Pharmacy, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China.
- 2. School of Pharmacy, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China; Department of Gastrointestinal and Pancreatic Surgery, Key Laboratory of Gastroenterology of Zhejiang Province, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang 310014, China.
- 3. Faculty of Chinese Medicine, National Key Laboratory of Mechanism and Quality of Chinese Medicines, Macau University of Science and Technology, Macau 999078, China; Zhuhai MUST Science and Technology Research Institute, Zhuhai 519031, China. Electronic address: [email protected].
- 4. Department of Gastrointestinal and Pancreatic Surgery, Key Laboratory of Gastroenterology of Zhejiang Province, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang 310014, China. Electronic address: [email protected].
- 5. School of Pharmacy, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China; Department of Gastrointestinal and Pancreatic Surgery, Key Laboratory of Gastroenterology of Zhejiang Province, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang 310014, China. Electronic address: [email protected].
- 6. School of Pharmacy, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China; Department of Gastrointestinal and Pancreatic Surgery, Key Laboratory of Gastroenterology of Zhejiang Province, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang 310014, China; Faculty of Chinese Medicine, National Key Laboratory of Mechanism and Quality of Chinese Medicines, Macau University of Science and Technology, Macau 999078, China. Electronic address: [email protected].
Pancreatic Cancer is a highly lethal malignancy with limited therapeutic options. Our study identifies butein, a natural chalcone from Plumbago species, as a powerful anti-tumor agent against pancreatic Cancer. Integrated in silico molecular docking and cellular biophysical assays, including Cellular Thermal Shift Assay (CETSA) and Drug Affinity Responsive Target Stability (DARTS), confirmed that CDK2 is a direct binding target of butein. Butein exerts its effects by arresting the cell cycle at the G2/M phase, inducing Apoptosis, and significantly inhibiting the proliferation of pancreatic Cancer cells. Further analysis revealed that butein downregulates CDK2 expression and disrupts its interaction with cyclinA2. Genetic validation confirmed CDK2 as the critical mediator of butein's efficacy that CDK2 overexpression conferred resistance, whereas its knockdown synergized with butein. In mouse xenograft models, butein treatment markedly inhibited tumor growth without observable systemic toxicity. Our findings highlight butein as a promising CDK2 Inhibitor, presenting a novel and translatable therapeutic strategy for pancreatic Cancer.