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Genipin suppression of growth and metastasis in hepatocellular carcinoma through blocking activation of STAT-3

Hong, Ming
; 
Lee, Selena
; 
Clayton, Jacob
; 
Yake, Wildman
; 
Li, Jinke
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Abstract
Background The signal transducer and activator of transcription-3 (STAT-3) can facilitate cancer progression and metastasis by being constitutively active via various signaling. Abundant evidence has indicated that STAT-3 may be a promising molecular target for cancer treatment. Methods In this study, a dual-luciferase assay-based screening of 537 compounds for STAT-3 inhibitors of hepatocellular carcinoma (HCC) cells was conducted, leading to the identification of genipin. Effects of genipin on HCC were assessed in a patient-derived xenograft nude mice model. Western blotting assay, chromatin immunoprecipitation (ChIP) assay, molecular docking study, tube formation assay, three-dimensional top culture assay, histological examination, and immunofluorescence were utilized to evaluate the regulatory signaling pathway. Results Our research demonstrated that genipin suppresses STAT-3 phosphorylation and nuclear translocation, which may be attributed to the binding capacity of this compound to the Src homology-2 (SH2) domain of STAT-3. In addition, the therapeutic effects of genipin in a patient-derived HCC xenograft nude mice model were also demonstrated. Conclusions In conclusion, genipin showed therapeutic potential for HCC treatment by interacting with the SH2-STAT-3 domain and suppressing the activity of STAT-3. In the future, further research is planned to explore the potential role of genipin in combination with chemotherapy or radiotherapy for HCC.
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This work is licensed under a Creative Commons Attribution 4.0 International License.
Date
2020-08-02
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BMC
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Pharmacy Scholarly Works
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Hong, M., Lee, S., Clayton, J., Yake, W., & Li, J. (2020). Genipin suppression of growth and metastasis in hepatocellular carcinoma through blocking activation of STAT-3. Journal of experimental & clinical cancer research : CR, 39(1), 146. https://doi.org/10.1186/s13046-020-01654-3
URI
https://hdl.handle.net/1808/30835
DOI
10.1186/s13046-020-01654-3
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