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Different Effects of Melatonin on X-Rays-Irradiated Cancer Cells in a Dose-Dependent Manner

The purpose of this study is to investigate the effects of melatonin on the radiosensitivity of HeLa cells. Concentration from 10 to 1000 µM of melatonin was used on HeLa cells before X-rays irradiation (IR). The cellular inactivation effect was analyzed by clonogenic assay, and cell growth was meas...

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Autores principales: Zhu, Hao, Chen, Yong, Bai, Liang-cai, Cao, Xiang-rong, Xu, Rui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE Publications 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6759722/
https://www.ncbi.nlm.nih.gov/pubmed/31579126
http://dx.doi.org/10.1177/1559325819877271
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author Zhu, Hao
Chen, Yong
Bai, Liang-cai
Cao, Xiang-rong
Xu, Rui
author_facet Zhu, Hao
Chen, Yong
Bai, Liang-cai
Cao, Xiang-rong
Xu, Rui
author_sort Zhu, Hao
collection PubMed
description The purpose of this study is to investigate the effects of melatonin on the radiosensitivity of HeLa cells. Concentration from 10 to 1000 µM of melatonin was used on HeLa cells before X-rays irradiation (IR). The cellular inactivation effect was analyzed by clonogenic assay, and cell growth was measured by MTT assay at various concentrations. Ten micrometer melatonin promoted the cell-killing effects of IR, while 1000-µM melatonin prevented IR-induced cellular inactivation. Further analysis revealed that 1000-µM melatonin protected the cells from IR-induced reactive oxygen species damage, as the oxidative stress measured by fluorescent microscopy and fluorescence-activated cell sorting using 2,7-dichlorofluorescein diacetate staining. This is further confirmed by melatonin receptor agonist, which has no antioxidant capacity. A 10-µM melatonin, on the contrary, enhanced the cell-killing effects of IR by activating c-Jun NH2-terminal kinase (JNK) signaling. c-Jun NH2-terminal kinase signaling activation was indicated by Western blot of phosphorylated JNK. We used JNK inhibitor to further confirm the involvement of JNK signaling in the cell-killing enhancement of 10-µM melatonin administration. Our results suggest the importance of dose-dependent effects in melatonin application for radiotherapy.
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spelling pubmed-67597222019-10-02 Different Effects of Melatonin on X-Rays-Irradiated Cancer Cells in a Dose-Dependent Manner Zhu, Hao Chen, Yong Bai, Liang-cai Cao, Xiang-rong Xu, Rui Dose Response Short Report The purpose of this study is to investigate the effects of melatonin on the radiosensitivity of HeLa cells. Concentration from 10 to 1000 µM of melatonin was used on HeLa cells before X-rays irradiation (IR). The cellular inactivation effect was analyzed by clonogenic assay, and cell growth was measured by MTT assay at various concentrations. Ten micrometer melatonin promoted the cell-killing effects of IR, while 1000-µM melatonin prevented IR-induced cellular inactivation. Further analysis revealed that 1000-µM melatonin protected the cells from IR-induced reactive oxygen species damage, as the oxidative stress measured by fluorescent microscopy and fluorescence-activated cell sorting using 2,7-dichlorofluorescein diacetate staining. This is further confirmed by melatonin receptor agonist, which has no antioxidant capacity. A 10-µM melatonin, on the contrary, enhanced the cell-killing effects of IR by activating c-Jun NH2-terminal kinase (JNK) signaling. c-Jun NH2-terminal kinase signaling activation was indicated by Western blot of phosphorylated JNK. We used JNK inhibitor to further confirm the involvement of JNK signaling in the cell-killing enhancement of 10-µM melatonin administration. Our results suggest the importance of dose-dependent effects in melatonin application for radiotherapy. SAGE Publications 2019-09-23 /pmc/articles/PMC6759722/ /pubmed/31579126 http://dx.doi.org/10.1177/1559325819877271 Text en © The Author(s) 2019 http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).
spellingShingle Short Report
Zhu, Hao
Chen, Yong
Bai, Liang-cai
Cao, Xiang-rong
Xu, Rui
Different Effects of Melatonin on X-Rays-Irradiated Cancer Cells in a Dose-Dependent Manner
title Different Effects of Melatonin on X-Rays-Irradiated Cancer Cells in a Dose-Dependent Manner
title_full Different Effects of Melatonin on X-Rays-Irradiated Cancer Cells in a Dose-Dependent Manner
title_fullStr Different Effects of Melatonin on X-Rays-Irradiated Cancer Cells in a Dose-Dependent Manner
title_full_unstemmed Different Effects of Melatonin on X-Rays-Irradiated Cancer Cells in a Dose-Dependent Manner
title_short Different Effects of Melatonin on X-Rays-Irradiated Cancer Cells in a Dose-Dependent Manner
title_sort different effects of melatonin on x-rays-irradiated cancer cells in a dose-dependent manner
topic Short Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6759722/
https://www.ncbi.nlm.nih.gov/pubmed/31579126
http://dx.doi.org/10.1177/1559325819877271
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