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Overexpression of CBS/H(2)S inhibits proliferation and metastasis of colon cancer cells through downregulation of CD44
BACKGROUND: The role of hydrogen sulfide (H(2)S) in cancer biology is controversial, including colorectal cancer. The bell-shaped effect of H(2)S refers to pro-cancer action at lower doses and anti-cancer effect at higher concentrations. We hypothesized that overexpression of cystathionine-beta-synt...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8848668/ https://www.ncbi.nlm.nih.gov/pubmed/35172821 http://dx.doi.org/10.1186/s12935-022-02512-2 |
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author | Zhang, Yuyang Chen, Shanwen Zhu, Jing Guo, Shihao Yue, Taohua Xu, Hao Hu, Jianwen Huang, Zhihao Chen, Zeyang Wang, Pengyuan Liu, Yucun |
author_facet | Zhang, Yuyang Chen, Shanwen Zhu, Jing Guo, Shihao Yue, Taohua Xu, Hao Hu, Jianwen Huang, Zhihao Chen, Zeyang Wang, Pengyuan Liu, Yucun |
author_sort | Zhang, Yuyang |
collection | PubMed |
description | BACKGROUND: The role of hydrogen sulfide (H(2)S) in cancer biology is controversial, including colorectal cancer. The bell-shaped effect of H(2)S refers to pro-cancer action at lower doses and anti-cancer effect at higher concentrations. We hypothesized that overexpression of cystathionine-beta-synthase (CBS)/H(2)S exerts an inhibitory effect on colon cancer cell proliferation and metastasis. METHODS: Cell proliferation was assessed by Cell Counting Kit-8 (CCK-8), clone-formation and sphere formation assay. Cell migration was evaluated by transwell migration assay. Intracellular H(2)S was detected by H(2)S probe. Chromatin immunoprecipitation (ChIP) analysis was carried out to examine DNA–protein interaction. Cell experiments also included western blotting, flow cytometry, immunohistochemistry (IHC) and immunofluorescence analysis. We further conducted in vivo experiments to confirm our conclusions. RESULTS: Overexpression of CBS and exogenous H(2)S inhibited colon cancer cell proliferation and migration in vitro. In addition, overexpression of CBS attenuated tumor growth and liver metastasis in vivo. Furthermore, CD44 and the transcription factor SP-1 was probably involved in the inhibitory effect of CBS/H(2)S axis on colon cancer cells. CONCLUSIONS: Overexpression of CBS and exogenous provision of H(2)S inhibited colon cancer cell proliferation and migration both in vivo and in vitro. Molecular mechanisms might involve the participation of CD44 and the transcription factor SP-1. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12935-022-02512-2. |
format | Online Article Text |
id | pubmed-8848668 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-88486682022-02-18 Overexpression of CBS/H(2)S inhibits proliferation and metastasis of colon cancer cells through downregulation of CD44 Zhang, Yuyang Chen, Shanwen Zhu, Jing Guo, Shihao Yue, Taohua Xu, Hao Hu, Jianwen Huang, Zhihao Chen, Zeyang Wang, Pengyuan Liu, Yucun Cancer Cell Int Primary Research BACKGROUND: The role of hydrogen sulfide (H(2)S) in cancer biology is controversial, including colorectal cancer. The bell-shaped effect of H(2)S refers to pro-cancer action at lower doses and anti-cancer effect at higher concentrations. We hypothesized that overexpression of cystathionine-beta-synthase (CBS)/H(2)S exerts an inhibitory effect on colon cancer cell proliferation and metastasis. METHODS: Cell proliferation was assessed by Cell Counting Kit-8 (CCK-8), clone-formation and sphere formation assay. Cell migration was evaluated by transwell migration assay. Intracellular H(2)S was detected by H(2)S probe. Chromatin immunoprecipitation (ChIP) analysis was carried out to examine DNA–protein interaction. Cell experiments also included western blotting, flow cytometry, immunohistochemistry (IHC) and immunofluorescence analysis. We further conducted in vivo experiments to confirm our conclusions. RESULTS: Overexpression of CBS and exogenous H(2)S inhibited colon cancer cell proliferation and migration in vitro. In addition, overexpression of CBS attenuated tumor growth and liver metastasis in vivo. Furthermore, CD44 and the transcription factor SP-1 was probably involved in the inhibitory effect of CBS/H(2)S axis on colon cancer cells. CONCLUSIONS: Overexpression of CBS and exogenous provision of H(2)S inhibited colon cancer cell proliferation and migration both in vivo and in vitro. Molecular mechanisms might involve the participation of CD44 and the transcription factor SP-1. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12935-022-02512-2. BioMed Central 2022-02-16 /pmc/articles/PMC8848668/ /pubmed/35172821 http://dx.doi.org/10.1186/s12935-022-02512-2 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Primary Research Zhang, Yuyang Chen, Shanwen Zhu, Jing Guo, Shihao Yue, Taohua Xu, Hao Hu, Jianwen Huang, Zhihao Chen, Zeyang Wang, Pengyuan Liu, Yucun Overexpression of CBS/H(2)S inhibits proliferation and metastasis of colon cancer cells through downregulation of CD44 |
title | Overexpression of CBS/H(2)S inhibits proliferation and metastasis of colon cancer cells through downregulation of CD44 |
title_full | Overexpression of CBS/H(2)S inhibits proliferation and metastasis of colon cancer cells through downregulation of CD44 |
title_fullStr | Overexpression of CBS/H(2)S inhibits proliferation and metastasis of colon cancer cells through downregulation of CD44 |
title_full_unstemmed | Overexpression of CBS/H(2)S inhibits proliferation and metastasis of colon cancer cells through downregulation of CD44 |
title_short | Overexpression of CBS/H(2)S inhibits proliferation and metastasis of colon cancer cells through downregulation of CD44 |
title_sort | overexpression of cbs/h(2)s inhibits proliferation and metastasis of colon cancer cells through downregulation of cd44 |
topic | Primary Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8848668/ https://www.ncbi.nlm.nih.gov/pubmed/35172821 http://dx.doi.org/10.1186/s12935-022-02512-2 |
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