Retraction Note: Endoplasmic reticulum stress triggers Xanthoangelol-induced protective autophagy via activation of JNK/c-Jun Axis in hepatocellular carcinoma
| Autor: | Kai-li Liu, Xianzhou Shi, Hui Gao, Zhuang Zhang, Kui Lu, Lifei Xing, Zhi Gong, Mei Han, Zichao Li, Mingquan Gao, Luying Zhang |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male Cancer Research Programmed cell death Carcinoma Hepatocellular MAP Kinase Signaling System Autolysosome ATG5 Cell Mice Nude Apoptosis lcsh:RC254-282 03 medical and health sciences Mice 0302 clinical medicine Chalcone medicine Autophagy Animals Humans HCC Endoplasmic Reticulum Chaperone BiP Cell Proliferation Chemistry Cell growth Research Intrinsic apoptosis Liver Neoplasms Proton Pump Inhibitors Endoplasmic Reticulum Stress lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens XAG 030104 developmental biology medicine.anatomical_structure Retraction Note Oncology 030220 oncology & carcinogenesis Cancer research ER stress |
| Zdroj: | Journal of Experimental & Clinical Cancer Research, Vol 39, Iss 1, Pp 1-2 (2020) Journal of Experimental & Clinical Cancer Research : CR |
| ISSN: | 1756-9966 |
| DOI: | 10.1186/s13046-020-01668-x |
| Popis: | Background Xanthoangelol (XAG) was reported to exhibit antitumor properties in several cancer. However, the specific anti-tumor activity of XAG in human hepatocellular carcinoma (HCC) and the relevant mechanisms are not known. Methods The effects of XAG on HCC cell proliferation and apoptosis were respectively examined by CCK-8 assay and Annexin V-FITC/PI apoptosis kit. Western blotting was conducted to detect the expression of proteins. The effect of XAG on the development of acidic vesicle organelles was assessed using acridine orange staining. mRFP-GFP-LC3 adenovirus was used to transfect HCC cells and the formation of autolysosome was detected using a confocal microscope. Results Mechanistically, XAG promotes HCC cell death through triggering intrinsic apoptosis pathway, not extrinsic apoptotic pathway. Furthermore, XAG treatment induced autophagy in Bel 7402 and SMMC 7721 cells, as evidenced by an increase in autophagy-associated proteins, including LC3B-II, Beclin-1, and Atg5. Interestingly, inhibition of autophagy with 3-MA, Bafilomycin A1 (Baf A1), or siRNA targeting Atg5 effectively enhanced the apoptotic cell ratio in XAG-treated cells, indicating that protective effect of autophagy induced by XAG in HCC. Moreover, autophagy induced by XAG was mediated by activating endoplasmic reticulum stress (ERS), along with administration of XAG, the expression levels of ERS-associated proteins, including CHOP, GRP78, ATF6, p-eIF2α, IRE1α, and cleaved caspase-12 were significantly increased in HCC cells. Meanwhile, suppressing ERS with chemical chaperones (TUDCA) or CHOP shRNA could effectively abrogate the autophagy-inducing effect of XAG, and increase the apoptotic cell death. Further mechanistic studies showed that ERS-induced autophagy in XAG-treated cells was mediated by activation of JNK/c-jun pathway. XAG treatment resulted in the increase of p-JNK and p-c-jun, while suppressing ERS with TUDCA or CHOP shRNA could effectively reverse it. Meanwhile, SP600125, a JNK inhibitor, effectively reversed XAG-induced protective autophagy and enhanced cell apoptosis in XAG-treated HCC cells. In vivo results demonstrated that XAG exerts potent antitumor properties with low toxicity. Conclusions Collectively, these results suggested that XAG could be served as a promising candidate for the treatment and prevention of HCC. Electronic supplementary material The online version of this article (10.1186/s13046-018-1012-z) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
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