Nobiletin suppresses cholangiocarcinoma proliferation via inhibiting GSK3β

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...

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Bibliographic Details
Published in:International journal of biological sciences 2022-01, Vol.18 (15), p.5698-5712
Main Authors: You, Liping, Lin, Jiacheng, Yu, Zhuo, Qian, Yihan, Bi, Yuting, Wang, Fang, Zhang, Lei, Zheng, Chao, Zhang, Jinghao, Li, Wenxuan, Cai, Yaxuan, Gao, Yueqiu, Kong, Xiaoni, Sun, Xuehua
Format: Article
Language:English
Subjects:
Animals
Antiproliferatives
Apoptosis
Bile Duct Neoplasms - drug therapy
Bile Duct Neoplasms - metabolism
Bile Duct Neoplasms - pathology
Bile ducts
Bile Ducts, Intrahepatic - metabolism
Bile Ducts, Intrahepatic - pathology
Cancer therapies
Cell cycle
Cell division
Cell growth
Cell Line, Tumor
Cell Proliferation
Cholangiocarcinoma
Cholangiocarcinoma - metabolism
Cyclin-dependent kinases
Flow cytometry
G1 phase
Glycogen Synthase Kinase 3 beta
Hepatotoxicity
Immunofluorescence
Kinases
Liver
Mice
Phosphorylation
Proteins
Research Paper
Tumors
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Summary: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. Our data showed that NBT suppressed CCA cell proliferation and . 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. 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.
ISSN:1449-2288
1449-2288
DOI:10.7150/ijbs.78345