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19-Hydroxybufalin Inhibits Gastric Cancer Cell Proliferation by Modulating Metabolic Reprogramming.
Xiao Liang1,2, Yilin Liu1, Xiaoting Ma3
1Department of Gastrointestinal Oncology, Jiangyin Clinical College of Xuzhou Medical University, Jiangyin 214400, China.
Journal of Proteome Research
|March 17, 2026
Summary
19-Hydroxybufalin (19-H) shows potent anticancer effects against gastric cancer by targeting PLPP2. This natural compound reshapes metabolic pathways, offering a potential new therapeutic strategy for this disease.
Area of Science:
- Pharmacology
- Oncology
- Biochemistry
Background:
- 19-Hydroxybufalin (19-H) is a natural compound with demonstrated anticancer properties.
- The precise molecular target and mechanism of action for 19-H's anticancer effects are not fully understood.
Purpose of the Study:
- To evaluate the anticancer activity of 19-Hydroxybufalin (19-H) against gastric cancer.
- To identify the molecular targets and elucidate the mechanism of action of 19-H in gastric cancer.
Main Methods:
- In vitro and in vivo studies assessed the antitumor effects of 19-H.
- Multiomics analysis, thermal proteome profiling (TPP), molecular docking, and molecular dynamics simulations were used.
- Functional assays validated the identified key molecular target.
Main Results:
- 19-H demonstrated nanomolar inhibitory activity against gastric cancer cell lines and suppressed tumor growth in vivo.
- Multiomics analysis indicated that 19-H alters metabolic pathways in gastric cancer.
- TPP identified PLPP2 as a direct binding target of 19-H, with stable binding confirmed by molecular simulations.
Conclusions:
- 19-Hydroxybufalin (19-H) exerts its gastric cancer-fighting effects through targeting PLPP2 and modulating the metabolic network.
- PLPP2 emerges as a potential novel therapeutic target for the treatment of gastric cancer.
