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Selective synergistic anticancer effects of cisplatin and oridonin against human p53-mutant esophageal squamous carcinoma cells

Oridonin (ORI) is known to pose anticancer activity against cancer, which could induce the therapeutic impact of chemotherapy drugs. However, such simple combinations have numerous side effects such as higher toxicity to normal cells and tissues. To enhance the therapeutic effects with minimal side...

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Autores principales: Yang, Huiyu, Wang, Jie, Khan, Suliman, Zhang, Yuanying, Zhu, Kuicheng, Zhou, Enhui, Gong, Meiyuan, Liu, Bingrong, Kan, Quancheng, Zhang, Qi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Lippincott Williams & Wilkins 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8670348/
https://www.ncbi.nlm.nih.gov/pubmed/34520434
http://dx.doi.org/10.1097/CAD.0000000000001237
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author Yang, Huiyu
Wang, Jie
Khan, Suliman
Zhang, Yuanying
Zhu, Kuicheng
Zhou, Enhui
Gong, Meiyuan
Liu, Bingrong
Kan, Quancheng
Zhang, Qi
author_facet Yang, Huiyu
Wang, Jie
Khan, Suliman
Zhang, Yuanying
Zhu, Kuicheng
Zhou, Enhui
Gong, Meiyuan
Liu, Bingrong
Kan, Quancheng
Zhang, Qi
author_sort Yang, Huiyu
collection PubMed
description Oridonin (ORI) is known to pose anticancer activity against cancer, which could induce the therapeutic impact of chemotherapy drugs. However, such simple combinations have numerous side effects such as higher toxicity to normal cells and tissues. To enhance the therapeutic effects with minimal side effects, here we used ORI in combination with cisplitin (CIS) against different esophageal squamous cell carcinoma (ESCC) cell lines in vitro, to investigate the synergistic anticancer effects of the two drugs against ESCC. Calcusyn Graphing Software was used to assess the synergistic effect. Apoptosis, wound healing and cell invasion assay were conducted to further confirm the synergistic effects of ORI and CIS. Intracellular glutathione (GSH) and reactive oxygen species assay, immunofluorescence staining and western blot were used to verify the mechanism of synergistic cytotoxicity. ORI and CIS pose selective synergistic effects on ESCC cells with p53 mutations. Moreover, we found that the synergistic effects of these drugs are mediated by GSH/ROS systems, such that intracellular GSH production was inhibited, whereas the ROS generation was induced following ORI and CIS application. In addition, we noted that DNA damage was induced as in response to ORI and CIS treatment. Overall, these results suggest that ORI can synergistically enhance the effect of CIS, and GSH deficiency and p53 mutation, might be biomarkers for the combinational usage of ORI and CIS.
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spelling pubmed-86703482021-12-15 Selective synergistic anticancer effects of cisplatin and oridonin against human p53-mutant esophageal squamous carcinoma cells Yang, Huiyu Wang, Jie Khan, Suliman Zhang, Yuanying Zhu, Kuicheng Zhou, Enhui Gong, Meiyuan Liu, Bingrong Kan, Quancheng Zhang, Qi Anticancer Drugs Pre-Clinical Reports Oridonin (ORI) is known to pose anticancer activity against cancer, which could induce the therapeutic impact of chemotherapy drugs. However, such simple combinations have numerous side effects such as higher toxicity to normal cells and tissues. To enhance the therapeutic effects with minimal side effects, here we used ORI in combination with cisplitin (CIS) against different esophageal squamous cell carcinoma (ESCC) cell lines in vitro, to investigate the synergistic anticancer effects of the two drugs against ESCC. Calcusyn Graphing Software was used to assess the synergistic effect. Apoptosis, wound healing and cell invasion assay were conducted to further confirm the synergistic effects of ORI and CIS. Intracellular glutathione (GSH) and reactive oxygen species assay, immunofluorescence staining and western blot were used to verify the mechanism of synergistic cytotoxicity. ORI and CIS pose selective synergistic effects on ESCC cells with p53 mutations. Moreover, we found that the synergistic effects of these drugs are mediated by GSH/ROS systems, such that intracellular GSH production was inhibited, whereas the ROS generation was induced following ORI and CIS application. In addition, we noted that DNA damage was induced as in response to ORI and CIS treatment. Overall, these results suggest that ORI can synergistically enhance the effect of CIS, and GSH deficiency and p53 mutation, might be biomarkers for the combinational usage of ORI and CIS. Lippincott Williams & Wilkins 2021-09-13 2022-01 /pmc/articles/PMC8670348/ /pubmed/34520434 http://dx.doi.org/10.1097/CAD.0000000000001237 Text en Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) , where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
spellingShingle Pre-Clinical Reports
Yang, Huiyu
Wang, Jie
Khan, Suliman
Zhang, Yuanying
Zhu, Kuicheng
Zhou, Enhui
Gong, Meiyuan
Liu, Bingrong
Kan, Quancheng
Zhang, Qi
Selective synergistic anticancer effects of cisplatin and oridonin against human p53-mutant esophageal squamous carcinoma cells
title Selective synergistic anticancer effects of cisplatin and oridonin against human p53-mutant esophageal squamous carcinoma cells
title_full Selective synergistic anticancer effects of cisplatin and oridonin against human p53-mutant esophageal squamous carcinoma cells
title_fullStr Selective synergistic anticancer effects of cisplatin and oridonin against human p53-mutant esophageal squamous carcinoma cells
title_full_unstemmed Selective synergistic anticancer effects of cisplatin and oridonin against human p53-mutant esophageal squamous carcinoma cells
title_short Selective synergistic anticancer effects of cisplatin and oridonin against human p53-mutant esophageal squamous carcinoma cells
title_sort selective synergistic anticancer effects of cisplatin and oridonin against human p53-mutant esophageal squamous carcinoma cells
topic Pre-Clinical Reports
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8670348/
https://www.ncbi.nlm.nih.gov/pubmed/34520434
http://dx.doi.org/10.1097/CAD.0000000000001237
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