ReferenceID 2658
Piceatannol enhances Beclin-1 activity to suppress tumor progression and its combination therapy strategy with everolimus in gastric cancer
Sci China Life Sci
The effects and regulation of Beclin-1-an autophagy-related protein-have not been fully defined, however, a negative correlation has been reported between Beclin-1 expression and carcinogenesis. Meanwhile, no compound ha
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Record Fields
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- Reference Id
- 2658
- Evidence Id
- 19248
- Core Evidence Id
- 19248
- Source Reference Id
- 5313
- Herb2 Reference Id
- HBREF006110
- Subject Paper Key
- HBIN040152_36271983
- Pubmed Id
- 36271983
- Doi
- 10.1007/s11427-022-2185-9
- Paper Title
- Piceatannol enhances Beclin-1 activity to suppress tumor progression and its combination therapy strategy with everolimus in gastric cancer
- Paper Abstract
- The effects and regulation of Beclin-1-an autophagy-related protein-have not been fully defined, however, a negative correlation has been reported between Beclin-1 expression and carcinogenesis. Meanwhile, no compound has been shown to directly inhibit its activity. Here, we evaluate piceatannol, a naturally occurring polyphenolic compound, as a potential targeting agonist of Beclin-1, to assess its efficacy as an antitumor agent against gastric cancer. More specifically, we determine the effects of piceatannol treatment on cell viability using a monitoring system and colony forming assay. Piceatannol was found to efficiently inhibit the proliferation of several human gastric cancer cell lines. Autophagic flux is increased by piceatannol treatment, and correlates with inhibition of cell proliferation and colony formation. Additionally, microscale thermophoresis and surface plasmon resonance results show a direct interaction between piceatannol and Beclin-1, which reduces the phosphorylation activity of Beclin-1 at the Ser-295 site. Notably, piceatannol impairs the binding of Beclin-1 to Bcl-2 and enhances the recruitment of binding of UV radiation resistance-associated gene protein, which further triggers Beclin-1-dependent autophagy signaling. An increase in autophagic activity via treatment with the mTOR inhibitor, everolimus, effectively sensitizes piceatannol-induced antitumor effects. Xenograft models confirmed that piceatannol inhibits tumor development and elicits a potent synergistic effect with everolimus in vivo. Taken together, the findings of this study strongly support the application of combinatorial piceatannol and everolimus therapy in future clinical trials for gastric cancer patients.
- Journal
- Sci China Life Sci
- Publish Year
- 2022
- Experiment Subject
- human; patient; human gastric cancer cell lines
- Experiment Type
- Cell Experiment
- Phenotype Related
- Gastric Cancer; Tumor
- Paper Title Cn
- Paper Title En
- Piceatannol enhances Beclin-1 activity to suppress tumor progression and its combination therapy strategy with everolimus in gastric cancer
- Bilingual Status
- semi_complete