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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...

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Autores principales: Yang, Rui-Yi, Tan, Jia-Yi, Liu, Zhe, Shen, Xiao-Ling, Hu, Ying-Jie
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
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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.
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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
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