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Radiosensitization of clioquinol and zinc in human cancer cell lines

BACKGROUND: We previously reported that clioquinol acts as a zinc ionophore and inhibits the NF-κB signalling pathway. Other research has demonstrated that zinc deficiency plays a vital role in the occurrence and development of some solid tumours, and intracellular zinc supplementation may reverse t...

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Autores principales: Lu, Shan, Ke, Yuan, Wu, Chaoyan, Zhong, Yahua, Xie, Conghua, Zhou, Yunfeng, Zhou, Fuxiang, Yu, Haijun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5910585/
https://www.ncbi.nlm.nih.gov/pubmed/29678153
http://dx.doi.org/10.1186/s12885-018-4264-2
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author Lu, Shan
Ke, Yuan
Wu, Chaoyan
Zhong, Yahua
Xie, Conghua
Zhou, Yunfeng
Zhou, Fuxiang
Yu, Haijun
author_facet Lu, Shan
Ke, Yuan
Wu, Chaoyan
Zhong, Yahua
Xie, Conghua
Zhou, Yunfeng
Zhou, Fuxiang
Yu, Haijun
author_sort Lu, Shan
collection PubMed
description BACKGROUND: We previously reported that clioquinol acts as a zinc ionophore and inhibits the NF-κB signalling pathway. Other research has demonstrated that zinc deficiency plays a vital role in the occurrence and development of some solid tumours, and intracellular zinc supplementation may reverse this process and enhance the tumour sensitivity to anticancer treatment. Thus, we investigated the radiosensitization effects of clioquinol combined with zinc on HeLa and MCF-7 cells in vitro. METHODS: The dose effect of growth inhibition of clioquinol combined with zinc on cell viability was determined by a cell counting kit 8 (CCK-8) assay. The radiosensitization effect of clioquinol combined with zinc and/or MG132 in HeLa and MCF-7 cells was detected by the clonogenic assay. The cell cycle distribution and apoptosis of clioquinol combined with zinc on HeLa cells were analyzed by flow cytometry. A luciferase reporter construct was used to study the effect of clioquinol combined with zinc on NF-κB activity in HeLa cells. DNA double-strand breaks were detected by immunofluorescence. The mRNA and protein levels of ATM were analyzed by quantitative real-time PCR and Western blotting, respectively. RESULTS: Our research showed that clioquinol combined with zinc markedly increased the radiosensitivity of HeLa and MCF-7 cells in low toxic concentrations and resulted in a post-irradiation decrease in G2 phase arrest and an increase in apoptosis. Clioquinol combined with zinc also inhibited NF-κB activation, decreased ATM expression and increased DNA double-strand breaks (DSBs) induced by ionizing radiation. CONCLUSIONS: These findings indicated that clioquinol combined with zinc enhanced the radiosensitivity of HeLa and MCF-7 cells by the down-regulation of ATM through the NF-κB signalling pathway.
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spelling pubmed-59105852018-05-02 Radiosensitization of clioquinol and zinc in human cancer cell lines Lu, Shan Ke, Yuan Wu, Chaoyan Zhong, Yahua Xie, Conghua Zhou, Yunfeng Zhou, Fuxiang Yu, Haijun BMC Cancer Research Article BACKGROUND: We previously reported that clioquinol acts as a zinc ionophore and inhibits the NF-κB signalling pathway. Other research has demonstrated that zinc deficiency plays a vital role in the occurrence and development of some solid tumours, and intracellular zinc supplementation may reverse this process and enhance the tumour sensitivity to anticancer treatment. Thus, we investigated the radiosensitization effects of clioquinol combined with zinc on HeLa and MCF-7 cells in vitro. METHODS: The dose effect of growth inhibition of clioquinol combined with zinc on cell viability was determined by a cell counting kit 8 (CCK-8) assay. The radiosensitization effect of clioquinol combined with zinc and/or MG132 in HeLa and MCF-7 cells was detected by the clonogenic assay. The cell cycle distribution and apoptosis of clioquinol combined with zinc on HeLa cells were analyzed by flow cytometry. A luciferase reporter construct was used to study the effect of clioquinol combined with zinc on NF-κB activity in HeLa cells. DNA double-strand breaks were detected by immunofluorescence. The mRNA and protein levels of ATM were analyzed by quantitative real-time PCR and Western blotting, respectively. RESULTS: Our research showed that clioquinol combined with zinc markedly increased the radiosensitivity of HeLa and MCF-7 cells in low toxic concentrations and resulted in a post-irradiation decrease in G2 phase arrest and an increase in apoptosis. Clioquinol combined with zinc also inhibited NF-κB activation, decreased ATM expression and increased DNA double-strand breaks (DSBs) induced by ionizing radiation. CONCLUSIONS: These findings indicated that clioquinol combined with zinc enhanced the radiosensitivity of HeLa and MCF-7 cells by the down-regulation of ATM through the NF-κB signalling pathway. BioMed Central 2018-04-20 /pmc/articles/PMC5910585/ /pubmed/29678153 http://dx.doi.org/10.1186/s12885-018-4264-2 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Lu, Shan
Ke, Yuan
Wu, Chaoyan
Zhong, Yahua
Xie, Conghua
Zhou, Yunfeng
Zhou, Fuxiang
Yu, Haijun
Radiosensitization of clioquinol and zinc in human cancer cell lines
title Radiosensitization of clioquinol and zinc in human cancer cell lines
title_full Radiosensitization of clioquinol and zinc in human cancer cell lines
title_fullStr Radiosensitization of clioquinol and zinc in human cancer cell lines
title_full_unstemmed Radiosensitization of clioquinol and zinc in human cancer cell lines
title_short Radiosensitization of clioquinol and zinc in human cancer cell lines
title_sort radiosensitization of clioquinol and zinc in human cancer cell lines
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5910585/
https://www.ncbi.nlm.nih.gov/pubmed/29678153
http://dx.doi.org/10.1186/s12885-018-4264-2
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