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WXJ-202, a novel Ribociclib derivative, exerts antitumor effects against breast cancer through CDK4/6

Cyclin-dependent kinases 4 and 6 (CDK4/6) are key regulatory proteins in the cell division and proliferative cycle in humans. They are overactive in many malignant tumors, particularly in triple-negative breast cancer (TNBC). Inhibition of CDK4/6 targets can have anti-tumor effects. Here, we designe...

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Autores principales: Ji, Jing, Liu, Wenwen, Xu, Yuxin, Xu, Zhou, Lv, Mingxiao, Feng, Jing, Lv, Jinyu, He, Xingbei, Zhang, Zhen, Xie, Mengru, Jing, Aixin, Wang, Xiujun, Ma, Jinming, Liu, Bin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9894725/
https://www.ncbi.nlm.nih.gov/pubmed/36744210
http://dx.doi.org/10.3389/fphar.2022.1072194
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author Ji, Jing
Liu, Wenwen
Xu, Yuxin
Xu, Zhou
Lv, Mingxiao
Feng, Jing
Lv, Jinyu
He, Xingbei
Zhang, Zhen
Xie, Mengru
Jing, Aixin
Wang, Xiujun
Ma, Jinming
Liu, Bin
author_facet Ji, Jing
Liu, Wenwen
Xu, Yuxin
Xu, Zhou
Lv, Mingxiao
Feng, Jing
Lv, Jinyu
He, Xingbei
Zhang, Zhen
Xie, Mengru
Jing, Aixin
Wang, Xiujun
Ma, Jinming
Liu, Bin
author_sort Ji, Jing
collection PubMed
description Cyclin-dependent kinases 4 and 6 (CDK4/6) are key regulatory proteins in the cell division and proliferative cycle in humans. They are overactive in many malignant tumors, particularly in triple-negative breast cancer (TNBC). Inhibition of CDK4/6 targets can have anti-tumor effects. Here, we designed and synthesized a novel derivative of Ribociclib that could affect CDK4/6, named WXJ-202. This study aimed to investigate the effects of compound WXJ-202 on proliferation, apoptosis, and cell cycle arrest in human breast cancer cell lines and their molecular mechanisms. We assayed cell viability with methyl thiazolyl tetrazolium (MTT) assay. Clone formation, migration, and invasion ability were assayed by clone formation assay, wound healing assay, and transwell invasion assay. The effect of compound WXJ-202 on apoptosis and cell cycle was detected by flow cytometry analysis. Western blotting was performed to detect the expression of proteins related to the CDK4/6-Rb-E2F pathway. The anti-cancer effects were studied in vivo transplantation tumor models. WXJ-202 was shown to inhibit cell proliferation, colony formation, migration, and invasion, as well as induce apoptosis and cycle arrest in breast cancer cells. The levels of proteins related to the CDK4/6-Rb-E2F pathway, such as CDK4, CDK6, and p-Rb, were decreased. Finally, studies had shown that compound WXJ-202 exhibited significant anti-tumor activity in transplantation tumor models. In this research, the compound WXJ-202 was shown to have better anti-tumor cell proliferative effects and could be used as a potential candidate against TNBC tumors.
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spelling pubmed-98947252023-02-03 WXJ-202, a novel Ribociclib derivative, exerts antitumor effects against breast cancer through CDK4/6 Ji, Jing Liu, Wenwen Xu, Yuxin Xu, Zhou Lv, Mingxiao Feng, Jing Lv, Jinyu He, Xingbei Zhang, Zhen Xie, Mengru Jing, Aixin Wang, Xiujun Ma, Jinming Liu, Bin Front Pharmacol Pharmacology Cyclin-dependent kinases 4 and 6 (CDK4/6) are key regulatory proteins in the cell division and proliferative cycle in humans. They are overactive in many malignant tumors, particularly in triple-negative breast cancer (TNBC). Inhibition of CDK4/6 targets can have anti-tumor effects. Here, we designed and synthesized a novel derivative of Ribociclib that could affect CDK4/6, named WXJ-202. This study aimed to investigate the effects of compound WXJ-202 on proliferation, apoptosis, and cell cycle arrest in human breast cancer cell lines and their molecular mechanisms. We assayed cell viability with methyl thiazolyl tetrazolium (MTT) assay. Clone formation, migration, and invasion ability were assayed by clone formation assay, wound healing assay, and transwell invasion assay. The effect of compound WXJ-202 on apoptosis and cell cycle was detected by flow cytometry analysis. Western blotting was performed to detect the expression of proteins related to the CDK4/6-Rb-E2F pathway. The anti-cancer effects were studied in vivo transplantation tumor models. WXJ-202 was shown to inhibit cell proliferation, colony formation, migration, and invasion, as well as induce apoptosis and cycle arrest in breast cancer cells. The levels of proteins related to the CDK4/6-Rb-E2F pathway, such as CDK4, CDK6, and p-Rb, were decreased. Finally, studies had shown that compound WXJ-202 exhibited significant anti-tumor activity in transplantation tumor models. In this research, the compound WXJ-202 was shown to have better anti-tumor cell proliferative effects and could be used as a potential candidate against TNBC tumors. Frontiers Media S.A. 2023-01-19 /pmc/articles/PMC9894725/ /pubmed/36744210 http://dx.doi.org/10.3389/fphar.2022.1072194 Text en Copyright © 2023 Ji, Liu, Xu, Xu, Lv, Feng, Lv, He, Zhang, Xie, Jing, Wang, Ma and Liu. 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 Pharmacology
Ji, Jing
Liu, Wenwen
Xu, Yuxin
Xu, Zhou
Lv, Mingxiao
Feng, Jing
Lv, Jinyu
He, Xingbei
Zhang, Zhen
Xie, Mengru
Jing, Aixin
Wang, Xiujun
Ma, Jinming
Liu, Bin
WXJ-202, a novel Ribociclib derivative, exerts antitumor effects against breast cancer through CDK4/6
title WXJ-202, a novel Ribociclib derivative, exerts antitumor effects against breast cancer through CDK4/6
title_full WXJ-202, a novel Ribociclib derivative, exerts antitumor effects against breast cancer through CDK4/6
title_fullStr WXJ-202, a novel Ribociclib derivative, exerts antitumor effects against breast cancer through CDK4/6
title_full_unstemmed WXJ-202, a novel Ribociclib derivative, exerts antitumor effects against breast cancer through CDK4/6
title_short WXJ-202, a novel Ribociclib derivative, exerts antitumor effects against breast cancer through CDK4/6
title_sort wxj-202, a novel ribociclib derivative, exerts antitumor effects against breast cancer through cdk4/6
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9894725/
https://www.ncbi.nlm.nih.gov/pubmed/36744210
http://dx.doi.org/10.3389/fphar.2022.1072194
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