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6-Methoxyflavone induces S-phase arrest through the CCNA2/CDK2/p21CIP1 signaling pathway in HeLa cells
This study aimed to elucidate the specific anticancer mechanism of 6-methoxyflavone in HeLa cells. A total of 178 putative targets of 6-methoxyflavone were obtained from the PharmMapper database. Microarray analyses, transcriptome sequencing analyses, functional enrichment analyses, and gene set enr...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Taylor & Francis
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8973872/ https://www.ncbi.nlm.nih.gov/pubmed/35246013 http://dx.doi.org/10.1080/21655979.2022.2047496 |
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author | Zhang, Chaihong Quan, Yuchong Yang, Lijuan Bai, Yingying Yang, Yongxiu |
author_facet | Zhang, Chaihong Quan, Yuchong Yang, Lijuan Bai, Yingying Yang, Yongxiu |
author_sort | Zhang, Chaihong |
collection | PubMed |
description | This study aimed to elucidate the specific anticancer mechanism of 6-methoxyflavone in HeLa cells. A total of 178 putative targets of 6-methoxyflavone were obtained from the PharmMapper database. Microarray analyses, transcriptome sequencing analyses, functional enrichment analyses, and gene set enrichment analyses were performed to preliminarily explore the roles and mechanisms of the 178 targets in cervical cancer. Cell counting kit-8, cell cycle assays, polymerase chain reactions, and western blotting were used to clarify the mechanism of action of 6-methoxyflavone. Molecular docking and noncovalent interaction analyses were performed to further confirm the mechanism of action in three-dimensional structures. Functional enrichment analyses and gene set enrichment analyses indicated that high mRNA expression of cyclin A2 (CCNA2) and cyclin-dependent kinase 2 (CDK2) stimulated cell cycle progression in cervical cancer. Cell proliferation and cycle assays, transcriptome sequencing, polymerase chain reactions, and western blotting revealed that 6-methoxyflavone inhibited HeLa cell proliferation and induced S-phase arrest via the CCNA2/CDK2/ cyclin-dependent kinase inhibitor 1A (p21CIP1) pathway. Molecular docking and noncovalent interaction analyses showed that 6-methoxyflavone had the strongest affinity toward, inhibitory effect on, and noncovalent interactions with CDK2, and that the combination of CDK2 and CCNA2 enhanced these effects. An analysis of clinical characteristics showed that 6-methoxyflavone might be related to six clinicopathological parameters of cervical cancer patients. 6-Methoxyflavone induces S-phase arrest in HeLa cells via the CCNA2/CDK2/p21CIP1 pathway. |
format | Online Article Text |
id | pubmed-8973872 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-89738722022-04-02 6-Methoxyflavone induces S-phase arrest through the CCNA2/CDK2/p21CIP1 signaling pathway in HeLa cells Zhang, Chaihong Quan, Yuchong Yang, Lijuan Bai, Yingying Yang, Yongxiu Bioengineered Research Paper This study aimed to elucidate the specific anticancer mechanism of 6-methoxyflavone in HeLa cells. A total of 178 putative targets of 6-methoxyflavone were obtained from the PharmMapper database. Microarray analyses, transcriptome sequencing analyses, functional enrichment analyses, and gene set enrichment analyses were performed to preliminarily explore the roles and mechanisms of the 178 targets in cervical cancer. Cell counting kit-8, cell cycle assays, polymerase chain reactions, and western blotting were used to clarify the mechanism of action of 6-methoxyflavone. Molecular docking and noncovalent interaction analyses were performed to further confirm the mechanism of action in three-dimensional structures. Functional enrichment analyses and gene set enrichment analyses indicated that high mRNA expression of cyclin A2 (CCNA2) and cyclin-dependent kinase 2 (CDK2) stimulated cell cycle progression in cervical cancer. Cell proliferation and cycle assays, transcriptome sequencing, polymerase chain reactions, and western blotting revealed that 6-methoxyflavone inhibited HeLa cell proliferation and induced S-phase arrest via the CCNA2/CDK2/ cyclin-dependent kinase inhibitor 1A (p21CIP1) pathway. Molecular docking and noncovalent interaction analyses showed that 6-methoxyflavone had the strongest affinity toward, inhibitory effect on, and noncovalent interactions with CDK2, and that the combination of CDK2 and CCNA2 enhanced these effects. An analysis of clinical characteristics showed that 6-methoxyflavone might be related to six clinicopathological parameters of cervical cancer patients. 6-Methoxyflavone induces S-phase arrest in HeLa cells via the CCNA2/CDK2/p21CIP1 pathway. Taylor & Francis 2022-03-04 /pmc/articles/PMC8973872/ /pubmed/35246013 http://dx.doi.org/10.1080/21655979.2022.2047496 Text en © 2022 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 Paper Zhang, Chaihong Quan, Yuchong Yang, Lijuan Bai, Yingying Yang, Yongxiu 6-Methoxyflavone induces S-phase arrest through the CCNA2/CDK2/p21CIP1 signaling pathway in HeLa cells |
title | 6-Methoxyflavone induces S-phase arrest through the CCNA2/CDK2/p21CIP1 signaling pathway in HeLa cells |
title_full | 6-Methoxyflavone induces S-phase arrest through the CCNA2/CDK2/p21CIP1 signaling pathway in HeLa cells |
title_fullStr | 6-Methoxyflavone induces S-phase arrest through the CCNA2/CDK2/p21CIP1 signaling pathway in HeLa cells |
title_full_unstemmed | 6-Methoxyflavone induces S-phase arrest through the CCNA2/CDK2/p21CIP1 signaling pathway in HeLa cells |
title_short | 6-Methoxyflavone induces S-phase arrest through the CCNA2/CDK2/p21CIP1 signaling pathway in HeLa cells |
title_sort | 6-methoxyflavone induces s-phase arrest through the ccna2/cdk2/p21cip1 signaling pathway in hela cells |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8973872/ https://www.ncbi.nlm.nih.gov/pubmed/35246013 http://dx.doi.org/10.1080/21655979.2022.2047496 |
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