Cargando…
Lappaol F regulates the cell cycle by activating CDKN1C/p57 in human colorectal cancer cells
CONTEXT: Lappaol F (LAF), a natural lignan from Arctium lappa Linné (Asteraceae), inhibits tumor cell growth in vitro and in vivo. The underlying mechanism involves the suppression of the Yes-associated protein. However, the specific role of LAF in cell cycle regulation remains unknown. OBJECTIVE: T...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Taylor & Francis
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9888477/ https://www.ncbi.nlm.nih.gov/pubmed/36708218 http://dx.doi.org/10.1080/13880209.2023.2172048 |
_version_ | 1784880540231401472 |
---|---|
author | Yang, Rui-Yi Tan, Jia-Yi Liu, Zhe Shen, Xiao-Ling Hu, Ying-Jie |
author_facet | Yang, Rui-Yi Tan, Jia-Yi Liu, Zhe Shen, Xiao-Ling Hu, Ying-Jie |
author_sort | Yang, Rui-Yi |
collection | PubMed |
description | CONTEXT: Lappaol F (LAF), a natural lignan from Arctium lappa Linné (Asteraceae), inhibits tumor cell growth in vitro and in vivo. The underlying mechanism involves the suppression of the Yes-associated protein. However, the specific role of LAF in cell cycle regulation remains unknown. OBJECTIVE: This study determined the molecular mechanism by which LAF regulates cell cycle progression. MATERIALS AND METHODS: Various colon cancer cell lines (SW480, HCT15, and HCT116) were treated with LAF (25, 50, and 75 μmol/L) for 48 h. The effects of LAF on cell proliferation and cell cycle were determined using sulforhodamine B and flow cytometry assays. Differentially expressed proteins (DEPs) were identified using quantitative proteomics. Bioinformatic analysis of DEPs was conducted via Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Expression levels of DEPs in the cell cycle pathway were analyzed using RT-qPCR and western blotting. RESULTS: LAF suppressed the proliferation of SW480, HCT15, and HCT116 cells (IC(50) 47.1, 51.4, and 32.8 μmol/L, respectively) and induced cell cycle arrest at the S phase. A total of 6331 proteins were identified and quantified, of which 127 were differentially expressed between the LAF-treated and untreated groups. GO and KEGG enrichment analyses revealed that DEPs mainly participated in the cell cycle. CDKN1C/p57 showed the most significant differential expression, with the highest fold-change (3.155-fold). Knockdown of CDKN1C/p57 attenuated the S phase cell cycle arrest and proliferation inhibition induced by LAF. CONCLUSION: LAF exerts antitumor effects via S phase arrest by activating CDKN1C/p57 in colorectal cancer cells. |
format | Online Article Text |
id | pubmed-9888477 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-98884772023-02-01 Lappaol F regulates the cell cycle by activating CDKN1C/p57 in human colorectal cancer cells Yang, Rui-Yi Tan, Jia-Yi Liu, Zhe Shen, Xiao-Ling Hu, Ying-Jie Pharm Biol Research Article CONTEXT: Lappaol F (LAF), a natural lignan from Arctium lappa Linné (Asteraceae), inhibits tumor cell growth in vitro and in vivo. The underlying mechanism involves the suppression of the Yes-associated protein. However, the specific role of LAF in cell cycle regulation remains unknown. OBJECTIVE: This study determined the molecular mechanism by which LAF regulates cell cycle progression. MATERIALS AND METHODS: Various colon cancer cell lines (SW480, HCT15, and HCT116) were treated with LAF (25, 50, and 75 μmol/L) for 48 h. The effects of LAF on cell proliferation and cell cycle were determined using sulforhodamine B and flow cytometry assays. Differentially expressed proteins (DEPs) were identified using quantitative proteomics. Bioinformatic analysis of DEPs was conducted via Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Expression levels of DEPs in the cell cycle pathway were analyzed using RT-qPCR and western blotting. RESULTS: LAF suppressed the proliferation of SW480, HCT15, and HCT116 cells (IC(50) 47.1, 51.4, and 32.8 μmol/L, respectively) and induced cell cycle arrest at the S phase. A total of 6331 proteins were identified and quantified, of which 127 were differentially expressed between the LAF-treated and untreated groups. GO and KEGG enrichment analyses revealed that DEPs mainly participated in the cell cycle. CDKN1C/p57 showed the most significant differential expression, with the highest fold-change (3.155-fold). Knockdown of CDKN1C/p57 attenuated the S phase cell cycle arrest and proliferation inhibition induced by LAF. CONCLUSION: LAF exerts antitumor effects via S phase arrest by activating CDKN1C/p57 in colorectal cancer cells. Taylor & Francis 2023-01-28 /pmc/articles/PMC9888477/ /pubmed/36708218 http://dx.doi.org/10.1080/13880209.2023.2172048 Text en © 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Yang, Rui-Yi Tan, Jia-Yi Liu, Zhe Shen, Xiao-Ling Hu, Ying-Jie Lappaol F regulates the cell cycle by activating CDKN1C/p57 in human colorectal cancer cells |
title | Lappaol F regulates the cell cycle by activating CDKN1C/p57 in human colorectal cancer cells |
title_full | Lappaol F regulates the cell cycle by activating CDKN1C/p57 in human colorectal cancer cells |
title_fullStr | Lappaol F regulates the cell cycle by activating CDKN1C/p57 in human colorectal cancer cells |
title_full_unstemmed | Lappaol F regulates the cell cycle by activating CDKN1C/p57 in human colorectal cancer cells |
title_short | Lappaol F regulates the cell cycle by activating CDKN1C/p57 in human colorectal cancer cells |
title_sort | lappaol f regulates the cell cycle by activating cdkn1c/p57 in human colorectal cancer cells |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9888477/ https://www.ncbi.nlm.nih.gov/pubmed/36708218 http://dx.doi.org/10.1080/13880209.2023.2172048 |
work_keys_str_mv | AT yangruiyi lappaolfregulatesthecellcyclebyactivatingcdkn1cp57inhumancolorectalcancercells AT tanjiayi lappaolfregulatesthecellcyclebyactivatingcdkn1cp57inhumancolorectalcancercells AT liuzhe lappaolfregulatesthecellcyclebyactivatingcdkn1cp57inhumancolorectalcancercells AT shenxiaoling lappaolfregulatesthecellcyclebyactivatingcdkn1cp57inhumancolorectalcancercells AT huyingjie lappaolfregulatesthecellcyclebyactivatingcdkn1cp57inhumancolorectalcancercells |