ReferenceID 939
Autophagic Inhibition of Caveolin-1 by Compound Phyllanthus urinaria L. Activates Ubiquitination and Proteasome Degradation of β-catenin to Suppress Metastasis of Hepatitis B-Associated Hepatocellular Carcinoma
Front Pharmacol
Compound Phyllanthus urinaria L. (CP) is a traditional Chinese medicine (TCM) formula for cancer treatment in the clinic, particularly during progression of hepatitis B-associated hepatocellular carcinoma (HBV-associated
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Record Fields
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- Reference Id
- 939
- Evidence Id
- 17529
- Core Evidence Id
- 17529
- Source Reference Id
- 1878
- Herb2 Reference Id
- HBREF002675
- Subject Paper Key
- HERB006492_34168559
- Pubmed Id
- 34168559
- Doi
- 10.3389/fphar.2021.659325
- Paper Title
- Autophagic Inhibition of Caveolin-1 by Compound Phyllanthus urinaria L. Activates Ubiquitination and Proteasome Degradation of β-catenin to Suppress Metastasis of Hepatitis B-Associated Hepatocellular Carcinoma
- Paper Abstract
- Compound Phyllanthus urinaria L. (CP) is a traditional Chinese medicine (TCM) formula for cancer treatment in the clinic, particularly during progression of hepatitis B-associated hepatocellular carcinoma (HBV-associated HCC). Nevertheless, its anti-metastatic action and mechanisms are not well elucidated. In this study, CP was found to exert remarkable inhibitory effects on the proliferation, migration and invasion of HBV-associated HCC cells. The following network and biological analyses predicted that CP mainly targeted Caveolin-1 (Cav-1) to induce anti-metastatic effects, and Wnt/beta-catenin pathway was one of the core mechanisms of CP action against HBV-associated HCC. Further experimental validation implied that Cav-1 overexpression promoted metastasis of HBV-associated HCC by stabilizing beta-catenin, while CP administration induced autophagic degradation of Cav-1, activated the Akt/GSK3beta-mediated proteasome degradation of beta-catenin via ubiquitination activation, and subsequently attenuated the metastasis-promoting effect of Cav-1. In addition, the anti-cancer and anti-metastatic action of CP was further confirmed by in vivo and ex vivo experiments. It was found that CP inhibited the tumor growth and metastasis of HBV-associated HCC in both mice liver cancer xenograft and zebrafish xenotransplantation models. Taken together, our study not only highlights the novel function of CP formula in suppressing metastasis of HBV-associated HCC, but it also addresses the critical role of Cav-1 in mediating Akt/GSK3beta/beta-catenin axis to control the late-phase of cancer progression.
- Journal
- Front Pharmacol
- Publish Year
- 2021
- Experiment Subject
- mouse; hbv-associated hcc cells
- Experiment Type
- Animal Experiment
- Phenotype Related
- Hbv-associated Hcc; Tumor; Liver Cancer; Hepatitis B-associated Hepatocellular Carcinoma; Cancer
- Paper Title Cn
- Paper Title En
- Autophagic Inhibition of Caveolin-1 by Compound Phyllanthus urinaria L. Activates Ubiquitination and Proteasome Degradation of β-catenin to Suppress Metastasis of Hepatitis B-Associated Hepatocellular Carcinoma
- Bilingual Status
- semi_complete