International journal of molecular sciences, 2022-05, Vol.23 (9), p.5102
2022
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- Autor(en) / Beteiligte
- Titel
- Suppression of the Proliferation of Huh7 Hepatoma Cells Involving the Downregulation of Mutant p53 Protein and Inactivation of the STAT 3 Pathway with Ailanthoidol
- Ist Teil von
- International journal of molecular sciences, 2022-05, Vol.23 (9), p.5102
- Ort / Verlag
- Switzerland: MDPI AG
- Erscheinungsjahr
- 2022
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Ailanthoidol (ATD) has been isolated from the barks of and displays anti-inflammatory, antioxidant, antiadipogenic, and antitumor promotion activities. Recently, we found that ATD suppressed TGF-β1-induced migration and invasion of HepG2 cells. In this report, we found that ATD exhibited more potent cytotoxicity in Huh7 hepatoma cells (mutant : Y220C) than in HepG2 cells (wild-type ). A trypan blue dye exclusion assay and colony assay showed ATD inhibited the growth of Huh7 cells. ATD also induced G1 arrest and reduced the expression of cyclin D1 and CDK2. Flow cytometry analysis with Annexin-V/PI staining demonstrated that ATD induced significant apoptosis in Huh7 cells. Moreover, ATD increased the expression of cleaved PARP and Bax and decreased the expression of procaspase 3/8 and Bcl-xL/Bcl-2. In addition, ATD decreased the expression of mutant p53 protein (mut ), which is associated with cell proliferation with the exploration of p53 siRNA transfection. Furthermore, ATD suppressed the phosphorylation of the signal transducer and activator of transcription 3 (STAT3) and the expression of mevalonate kinase (MVK). Consistent with ATD, the administration of S3I201 (STAT 3 inhibitor) reduced the expression of Bcl-2/Bcl-xL, cyclin D1, mutp53, and MVK. These results demonstrated ATD's selectivity against mut hepatoma cells involving the downregulation of mut and inactivation of STAT3.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1422-0067, 1661-6596eISSN: 1422-0067DOI: 10.3390/ijms23095102Titel-ID: cdi_doaj_primary_oai_doaj_org_article_ceee36cc352045ec9213e918c8655449
- Format
- –
- Schlagworte
- ailanthoidol, Antioxidants, Apoptosis, Apoptosis - physiology, BAX protein, Bcl-2 protein, Bcl-x protein, Benzofurans, Cancer therapies, Carcinoma, Hepatocellular - genetics, Carcinoma, Hepatocellular - metabolism, cell cycle, Cell Line, Tumor, Cell Proliferation, Cyclin D1, Cyclin D1 - metabolism, Cytotoxicity, Down-Regulation, Flow cytometry, Hepatoma, Humans, Inflammation, Kinases, Liver cancer, Liver Neoplasms - genetics, Liver Neoplasms - metabolism, Mevalonate kinase, Mevalonic acid, mutant p53, Mutant Proteins - metabolism, Mutants, Mutation, p53 Protein, Phosphorylation, Poly(ADP-ribose) polymerase, Proteins, Proto-Oncogene Proteins c-bcl-2 - metabolism, Selectivity, Signal Transduction, siRNA, STAT3, Stat3 protein, Transfection, Transforming growth factor-b1, Tumor Suppressor Protein p53 - metabolism