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Xanthatin Selectively Targets Retinoblastoma by Inhibiting the PLK1-Mediated Cell Cycle

PURPOSE: Retinoblastoma is the most common primary intraocular malignant tumor in children. Although intra-arterial chemotherapy and conventional chemotherapy have become promising therapeutic approaches for advanced intraocular retinoblastoma, the side effects threaten health and are unavoidable, m...

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Autores principales: Yang, Jie, Li, Yongyun, Zong, Chunyan, Zhang, Qianqian, Ge, Shengfang, Ma, Lei, Fan, Jiayan, Zhang, Jianming, Jia, Renbing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Association for Research in Vision and Ophthalmology 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8684308/
https://www.ncbi.nlm.nih.gov/pubmed/34901994
http://dx.doi.org/10.1167/iovs.62.15.11
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author Yang, Jie
Li, Yongyun
Zong, Chunyan
Zhang, Qianqian
Ge, Shengfang
Ma, Lei
Fan, Jiayan
Zhang, Jianming
Jia, Renbing
author_facet Yang, Jie
Li, Yongyun
Zong, Chunyan
Zhang, Qianqian
Ge, Shengfang
Ma, Lei
Fan, Jiayan
Zhang, Jianming
Jia, Renbing
author_sort Yang, Jie
collection PubMed
description PURPOSE: Retinoblastoma is the most common primary intraocular malignant tumor in children. Although intra-arterial chemotherapy and conventional chemotherapy have become promising therapeutic approaches for advanced intraocular retinoblastoma, the side effects threaten health and are unavoidable, making the development of targeted therapy an urgent need. Therefore, we intended to find a potential drug for human retinoblastoma by screening an in-house compound library that included 89 purified and well-characterized natural products. METHODS: We screened a panel of 89 natural products in retinoblastoma cell lines to find the inhibitor. The inhibition of the identified inhibitor xanthatin on cell growth was detected through half-maximal inhibitory concentration (IC(50)), flow cytometry assay, and zebrafish model system. RNA-seq further selected the target gene PLK1. RESULTS: We reported the discovery of xanthatin as an effective inhibitor of retinoblastoma. Mechanistically, xanthatin selectively inhibited the proliferation of retinoblastoma cells by inducing cell cycle arrest and promoting apoptosis. Interestingly, xanthatin targeted PLK1-mediated cell cycle progression. The efficacy of xanthatin was further confirmed in zebrafish models. CONCLUSIONS: Collectively, our data suggested that xanthatin significantly inhibited tumor growth in vitro and in vivo, and xanthatin could be a potential drug treatment for retinoblastoma.
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spelling pubmed-86843082022-01-06 Xanthatin Selectively Targets Retinoblastoma by Inhibiting the PLK1-Mediated Cell Cycle Yang, Jie Li, Yongyun Zong, Chunyan Zhang, Qianqian Ge, Shengfang Ma, Lei Fan, Jiayan Zhang, Jianming Jia, Renbing Invest Ophthalmol Vis Sci Retina PURPOSE: Retinoblastoma is the most common primary intraocular malignant tumor in children. Although intra-arterial chemotherapy and conventional chemotherapy have become promising therapeutic approaches for advanced intraocular retinoblastoma, the side effects threaten health and are unavoidable, making the development of targeted therapy an urgent need. Therefore, we intended to find a potential drug for human retinoblastoma by screening an in-house compound library that included 89 purified and well-characterized natural products. METHODS: We screened a panel of 89 natural products in retinoblastoma cell lines to find the inhibitor. The inhibition of the identified inhibitor xanthatin on cell growth was detected through half-maximal inhibitory concentration (IC(50)), flow cytometry assay, and zebrafish model system. RNA-seq further selected the target gene PLK1. RESULTS: We reported the discovery of xanthatin as an effective inhibitor of retinoblastoma. Mechanistically, xanthatin selectively inhibited the proliferation of retinoblastoma cells by inducing cell cycle arrest and promoting apoptosis. Interestingly, xanthatin targeted PLK1-mediated cell cycle progression. The efficacy of xanthatin was further confirmed in zebrafish models. CONCLUSIONS: Collectively, our data suggested that xanthatin significantly inhibited tumor growth in vitro and in vivo, and xanthatin could be a potential drug treatment for retinoblastoma. The Association for Research in Vision and Ophthalmology 2021-12-13 /pmc/articles/PMC8684308/ /pubmed/34901994 http://dx.doi.org/10.1167/iovs.62.15.11 Text en Copyright 2021 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
spellingShingle Retina
Yang, Jie
Li, Yongyun
Zong, Chunyan
Zhang, Qianqian
Ge, Shengfang
Ma, Lei
Fan, Jiayan
Zhang, Jianming
Jia, Renbing
Xanthatin Selectively Targets Retinoblastoma by Inhibiting the PLK1-Mediated Cell Cycle
title Xanthatin Selectively Targets Retinoblastoma by Inhibiting the PLK1-Mediated Cell Cycle
title_full Xanthatin Selectively Targets Retinoblastoma by Inhibiting the PLK1-Mediated Cell Cycle
title_fullStr Xanthatin Selectively Targets Retinoblastoma by Inhibiting the PLK1-Mediated Cell Cycle
title_full_unstemmed Xanthatin Selectively Targets Retinoblastoma by Inhibiting the PLK1-Mediated Cell Cycle
title_short Xanthatin Selectively Targets Retinoblastoma by Inhibiting the PLK1-Mediated Cell Cycle
title_sort xanthatin selectively targets retinoblastoma by inhibiting the plk1-mediated cell cycle
topic Retina
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8684308/
https://www.ncbi.nlm.nih.gov/pubmed/34901994
http://dx.doi.org/10.1167/iovs.62.15.11
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