RETRACTED ARTICLE: Genipin suppression of growth and metastasis in hepatocellular carcinoma through blocking activation of STAT-3
Authors: Wildman Yake
Jinke Li
Jacob Clayton
Ming Hong
Selena Lee
Journal: Journal of Experimental & Clinical Cancer Research (2020)
Discipline: CLINICAL MEDICINE
Keywords: STAT-3; inhibitors; hepatocellular carcinoma; genipin; phosphorylation
Affiliations: Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, China. ., Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, Guangzhou, China. ., Department of Pharmacology & Toxicology, University of Kansas, Lawrence, KS, USA. ., Department of Pharmacology & Toxicology, University of Kansas, Lawrence, KS, USA.

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. 

Retracted: Yes

PubPeer comments:
 Retracted [15 March 2022] . -------------------------- The Editor-in-Chief has retracted this article. After publication concerns were raised with respect to the overlap of figures with a previously published article from another author group [1]. Specifically: - Figure 1b, 1c, 1d, 1e and 1f with Figure 1c, 1d, 1e, 1f and 1h of Figure 1 of [1] - Figure 2 with Figure 2 of [1] - Figure 3b and 3c with Figure 3b and 3d of [1] - Figure 4b, 4c and 4d with Figure 4b, 4c and 4d of [1] - Figure 5 with Figure 5 of [1] - Figure 6 with Figure 6 of [1] - Figure 7 with Figure 7 of [1] The Editor-in-Chief no longer has confidence in the results and conclusions reported. Ming Hong agrees with this retraction. Jacob Clayton, Wildman Yake and Jinke Li have not responded to correspondence from the Publisher about this retraction. The Publisher was not able to obtain a current email address for Selena Lee. - [1] Zhang T, Li J, Yin F, et al. Toosendanin demonstrates promising antitumor efficacy in osteosarcoma by targeting STAT3. Oncogene. 2017;36:6627u201339. ,