ReferenceID 5874
Nobiletin suppresses cholangiocarcinoma proliferation via inhibiting GSK3β
Int J Biol Sci
Background: Cholangiocarcinoma (CCA) is a type of hepatobiliary cancer characterized by uncontrolled cell proliferation, with a poor prognosis and high mortality. Nobiletin (NBT) is a promising anti-tumor compound derive
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Record Fields
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- Reference Id
- 5874
- Evidence Id
- 22464
- Core Evidence Id
- 22464
- Source Reference Id
- 5016
- Herb2 Reference Id
- HBREF005813
- Subject Paper Key
- HBIN037171_36263164
- Pubmed Id
- 36263164
- Doi
- 10.7150/ijbs.78345
- Paper Title
- Nobiletin suppresses cholangiocarcinoma proliferation via inhibiting GSK3β
- Paper Abstract
- Background: Cholangiocarcinoma (CCA) is a type of hepatobiliary cancer characterized by uncontrolled cell proliferation, with a poor prognosis and high mortality. Nobiletin (NBT) is a promising anti-tumor compound derived from the peels of oranges and other citrus plants, citrus plant. But the effect of NBT on CCA remains unknown. Results: Our data showed that NBT suppressed CCA cell proliferation in vitro and in vivo . Colony formation and Edu assay indicated that NBT inhibited cell proliferation. Cell cycle analysis showed that NBT arrested the cell cycle in G0/G1 phase. Target prediction showed that GSK3β was a direct target. Western blot and immunofluorescence confirmed that NBT reduced the phosphorylation of GSK3β. The antiproliferative effect of NBT was intercepted in GSK3β knockdown CCA cells. The cellular thermal shift assay (CETSA) showed NBT directly bound to GSK3β. Finally, NBT showed an anti-proliferative effect in tumor-bearing mice with no hepatotoxicity. Conclusion: NBT could inhibit CCA proliferation, and the pharmacological activity of NBT in CCA was attributed to its direct binding to GSK3β. We suggested that NBT might be a potential natural medicine in CCA treatment.
- Journal
- Int J Biol Sci
- Publish Year
- 2022
- Experiment Subject
- mouse; cca cell; gsk3β knockdown cca cells
- Experiment Type
- Animal & Cell Experiment
- Phenotype Related
- Hepatobiliary Cancer; Cholangiocarcinoma
- Paper Title Cn
- Paper Title En
- Nobiletin suppresses cholangiocarcinoma proliferation via inhibiting GSK3β
- Bilingual Status
- semi_complete