Unknown

Dataset Information

0

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


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.

SUBMITTER: Hong M 

PROVIDER: S-EPMC7397684 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

altmetric image

Publications

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

Hong Ming M   Lee Selena S   Clayton Jacob J   Yake Wildman W   Li Jinke J  

Journal of experimental & clinical cancer research : CR 20200802 1


<h4>Background</h4>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.<h4>Methods</h4>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. Effect  ...[more]

Similar Datasets

| S-EPMC5190038 | biostudies-literature
| S-EPMC8024385 | biostudies-literature
| S-EPMC7997956 | biostudies-literature
| S-EPMC7875922 | biostudies-literature
| S-EPMC6541593 | biostudies-literature
| S-EPMC4414157 | biostudies-literature
| S-EPMC5986742 | biostudies-literature
| S-EPMC7346057 | biostudies-literature
| S-EPMC7812266 | biostudies-literature
| S-EPMC5574939 | biostudies-literature