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Dihydroartemisinin Suppresses the Tumorigenesis and Cycle Progression of Colorectal Cancer by Targeting CDK1/CCNB1/PLK1 Signaling

Dihydroartemisinin (DHA), a well-known antimalarial drug, has been widely investigated for its antitumor effects in multiple malignancies. However, its effects and regulatory mechanisms in colorectal cancer (CRC) are still unproved. In this study, in vitro experiments including CCK8, EdU, Transwell,...

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Autores principales: Yi, You-Cai, Liang, Rui, Chen, Xiao-Yu, Fan, Hui-Ning, Chen, Ming, Zhang, Jing, Zhu, Jin-Shui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8592930/
https://www.ncbi.nlm.nih.gov/pubmed/34796115
http://dx.doi.org/10.3389/fonc.2021.768879
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author Yi, You-Cai
Liang, Rui
Chen, Xiao-Yu
Fan, Hui-Ning
Chen, Ming
Zhang, Jing
Zhu, Jin-Shui
author_facet Yi, You-Cai
Liang, Rui
Chen, Xiao-Yu
Fan, Hui-Ning
Chen, Ming
Zhang, Jing
Zhu, Jin-Shui
author_sort Yi, You-Cai
collection PubMed
description Dihydroartemisinin (DHA), a well-known antimalarial drug, has been widely investigated for its antitumor effects in multiple malignancies. However, its effects and regulatory mechanisms in colorectal cancer (CRC) are still unproved. In this study, in vitro experiments including CCK8, EdU, Transwell, and flow cytometry analyses and an in vivo tumorigenesis model were conducted to assess the effects of DHA on the bio-behaviors of CRC cells. Additionally, RNA-seq combined with gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses was used to obtain the targets of DHA, and these were verified by molecular docking, qRT-PCR, and Western blotting. As a result, we found that DHA significantly suppressed the proliferation, DNA synthesis, and invasive capabilities and induced cell apoptosis and cell cycle arrest in HCT116, DLD1, and RKO cells in vitro and in vivo. Further analyses indicated that the targets of DHA were predominantly enriched in cell cycle-associated pathways, including CDK1, CCNB1, and PLK1; and DHA could bind with the CDK1/CCNB1 complex and inhibit the activation of CDK1/CCNB1/PLK1 signaling. Moreover, cucurbitacin E, a specific inhibitor of the CDK1/CCNB1 axis, enhanced the inhibitory effects of DHA on DNA synthesis and colony formation in HCT116 and DLD1 cells. In short, DHA could suppress the tumorigenesis and cycle progression of CRC cells by targeting CDK1/CCNB1/PLK1 signaling.
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spelling pubmed-85929302021-11-17 Dihydroartemisinin Suppresses the Tumorigenesis and Cycle Progression of Colorectal Cancer by Targeting CDK1/CCNB1/PLK1 Signaling Yi, You-Cai Liang, Rui Chen, Xiao-Yu Fan, Hui-Ning Chen, Ming Zhang, Jing Zhu, Jin-Shui Front Oncol Oncology Dihydroartemisinin (DHA), a well-known antimalarial drug, has been widely investigated for its antitumor effects in multiple malignancies. However, its effects and regulatory mechanisms in colorectal cancer (CRC) are still unproved. In this study, in vitro experiments including CCK8, EdU, Transwell, and flow cytometry analyses and an in vivo tumorigenesis model were conducted to assess the effects of DHA on the bio-behaviors of CRC cells. Additionally, RNA-seq combined with gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses was used to obtain the targets of DHA, and these were verified by molecular docking, qRT-PCR, and Western blotting. As a result, we found that DHA significantly suppressed the proliferation, DNA synthesis, and invasive capabilities and induced cell apoptosis and cell cycle arrest in HCT116, DLD1, and RKO cells in vitro and in vivo. Further analyses indicated that the targets of DHA were predominantly enriched in cell cycle-associated pathways, including CDK1, CCNB1, and PLK1; and DHA could bind with the CDK1/CCNB1 complex and inhibit the activation of CDK1/CCNB1/PLK1 signaling. Moreover, cucurbitacin E, a specific inhibitor of the CDK1/CCNB1 axis, enhanced the inhibitory effects of DHA on DNA synthesis and colony formation in HCT116 and DLD1 cells. In short, DHA could suppress the tumorigenesis and cycle progression of CRC cells by targeting CDK1/CCNB1/PLK1 signaling. Frontiers Media S.A. 2021-11-02 /pmc/articles/PMC8592930/ /pubmed/34796115 http://dx.doi.org/10.3389/fonc.2021.768879 Text en Copyright © 2021 Yi, Liang, Chen, Fan, Chen, Zhang and Zhu https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Yi, You-Cai
Liang, Rui
Chen, Xiao-Yu
Fan, Hui-Ning
Chen, Ming
Zhang, Jing
Zhu, Jin-Shui
Dihydroartemisinin Suppresses the Tumorigenesis and Cycle Progression of Colorectal Cancer by Targeting CDK1/CCNB1/PLK1 Signaling
title Dihydroartemisinin Suppresses the Tumorigenesis and Cycle Progression of Colorectal Cancer by Targeting CDK1/CCNB1/PLK1 Signaling
title_full Dihydroartemisinin Suppresses the Tumorigenesis and Cycle Progression of Colorectal Cancer by Targeting CDK1/CCNB1/PLK1 Signaling
title_fullStr Dihydroartemisinin Suppresses the Tumorigenesis and Cycle Progression of Colorectal Cancer by Targeting CDK1/CCNB1/PLK1 Signaling
title_full_unstemmed Dihydroartemisinin Suppresses the Tumorigenesis and Cycle Progression of Colorectal Cancer by Targeting CDK1/CCNB1/PLK1 Signaling
title_short Dihydroartemisinin Suppresses the Tumorigenesis and Cycle Progression of Colorectal Cancer by Targeting CDK1/CCNB1/PLK1 Signaling
title_sort dihydroartemisinin suppresses the tumorigenesis and cycle progression of colorectal cancer by targeting cdk1/ccnb1/plk1 signaling
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8592930/
https://www.ncbi.nlm.nih.gov/pubmed/34796115
http://dx.doi.org/10.3389/fonc.2021.768879
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