Cargando…
Suppression of the Proliferation of Huh7 Hepatoma Cells Involving the Downregulation of Mutant p53 Protein and Inactivation of the STAT 3 Pathway with Ailanthoidol
Ailanthoidol (ATD) has been isolated from the barks of Zanthoxylum ailanthoides 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...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9099615/ https://www.ncbi.nlm.nih.gov/pubmed/35563493 http://dx.doi.org/10.3390/ijms23095102 |
_version_ | 1784706649811845120 |
---|---|
author | Tseng, Tsui-Hwa Wang, Chau-Jong Lee, Yean-Jang Shao, Yi-Chia Shen, Chien-Heng Lee, Ko-Chao Tung, Shui-Yi Kuo, Hsing-Chun |
author_facet | Tseng, Tsui-Hwa Wang, Chau-Jong Lee, Yean-Jang Shao, Yi-Chia Shen, Chien-Heng Lee, Ko-Chao Tung, Shui-Yi Kuo, Hsing-Chun |
author_sort | Tseng, Tsui-Hwa |
collection | PubMed |
description | Ailanthoidol (ATD) has been isolated from the barks of Zanthoxylum ailanthoides 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 p53: Y220C) than in HepG2 cells (wild-type p53). 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 (mutp53), 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 mutp53 hepatoma cells involving the downregulation of mutp53 and inactivation of STAT3. |
format | Online Article Text |
id | pubmed-9099615 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-90996152022-05-14 Suppression of the Proliferation of Huh7 Hepatoma Cells Involving the Downregulation of Mutant p53 Protein and Inactivation of the STAT 3 Pathway with Ailanthoidol Tseng, Tsui-Hwa Wang, Chau-Jong Lee, Yean-Jang Shao, Yi-Chia Shen, Chien-Heng Lee, Ko-Chao Tung, Shui-Yi Kuo, Hsing-Chun Int J Mol Sci Article Ailanthoidol (ATD) has been isolated from the barks of Zanthoxylum ailanthoides 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 p53: Y220C) than in HepG2 cells (wild-type p53). 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 (mutp53), 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 mutp53 hepatoma cells involving the downregulation of mutp53 and inactivation of STAT3. MDPI 2022-05-04 /pmc/articles/PMC9099615/ /pubmed/35563493 http://dx.doi.org/10.3390/ijms23095102 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Tseng, Tsui-Hwa Wang, Chau-Jong Lee, Yean-Jang Shao, Yi-Chia Shen, Chien-Heng Lee, Ko-Chao Tung, Shui-Yi Kuo, Hsing-Chun Suppression of the Proliferation of Huh7 Hepatoma Cells Involving the Downregulation of Mutant p53 Protein and Inactivation of the STAT 3 Pathway with Ailanthoidol |
title | Suppression of the Proliferation of Huh7 Hepatoma Cells Involving the Downregulation of Mutant p53 Protein and Inactivation of the STAT 3 Pathway with Ailanthoidol |
title_full | Suppression of the Proliferation of Huh7 Hepatoma Cells Involving the Downregulation of Mutant p53 Protein and Inactivation of the STAT 3 Pathway with Ailanthoidol |
title_fullStr | Suppression of the Proliferation of Huh7 Hepatoma Cells Involving the Downregulation of Mutant p53 Protein and Inactivation of the STAT 3 Pathway with Ailanthoidol |
title_full_unstemmed | Suppression of the Proliferation of Huh7 Hepatoma Cells Involving the Downregulation of Mutant p53 Protein and Inactivation of the STAT 3 Pathway with Ailanthoidol |
title_short | Suppression of the Proliferation of Huh7 Hepatoma Cells Involving the Downregulation of Mutant p53 Protein and Inactivation of the STAT 3 Pathway with Ailanthoidol |
title_sort | suppression of the proliferation of huh7 hepatoma cells involving the downregulation of mutant p53 protein and inactivation of the stat 3 pathway with ailanthoidol |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9099615/ https://www.ncbi.nlm.nih.gov/pubmed/35563493 http://dx.doi.org/10.3390/ijms23095102 |
work_keys_str_mv | AT tsengtsuihwa suppressionoftheproliferationofhuh7hepatomacellsinvolvingthedownregulationofmutantp53proteinandinactivationofthestat3pathwaywithailanthoidol AT wangchaujong suppressionoftheproliferationofhuh7hepatomacellsinvolvingthedownregulationofmutantp53proteinandinactivationofthestat3pathwaywithailanthoidol AT leeyeanjang suppressionoftheproliferationofhuh7hepatomacellsinvolvingthedownregulationofmutantp53proteinandinactivationofthestat3pathwaywithailanthoidol AT shaoyichia suppressionoftheproliferationofhuh7hepatomacellsinvolvingthedownregulationofmutantp53proteinandinactivationofthestat3pathwaywithailanthoidol AT shenchienheng suppressionoftheproliferationofhuh7hepatomacellsinvolvingthedownregulationofmutantp53proteinandinactivationofthestat3pathwaywithailanthoidol AT leekochao suppressionoftheproliferationofhuh7hepatomacellsinvolvingthedownregulationofmutantp53proteinandinactivationofthestat3pathwaywithailanthoidol AT tungshuiyi suppressionoftheproliferationofhuh7hepatomacellsinvolvingthedownregulationofmutantp53proteinandinactivationofthestat3pathwaywithailanthoidol AT kuohsingchun suppressionoftheproliferationofhuh7hepatomacellsinvolvingthedownregulationofmutantp53proteinandinactivationofthestat3pathwaywithailanthoidol |