Plumbagin Enhances the Anticancer Efficacy of Cisplatin by Increasing Intracellular ROS in Human Tongue Squamous Cell Carcinoma

Cisplatin is widely used in the treatment of tongue squamous cell carcinoma (TSCC), but its clinical efficacy is limited by drug resistance and toxic side effects. Hence, a novel compound capable of enhancing the anticancer effect of cisplatin while reducing the side effects is urgently needed. We h...

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Autores principales: Xue, Danfeng, Pan, Shu-Ting, Zhou, Xiongming, Ye, Fangfei, Zhou, Qun, Shi, Fanzhe, He, Fei, Yu, Hui, Qiu, Jiaxuan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7136784/
https://www.ncbi.nlm.nih.gov/pubmed/32308804
http://dx.doi.org/10.1155/2020/5649174
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author Xue, Danfeng
Pan, Shu-Ting
Zhou, Xiongming
Ye, Fangfei
Zhou, Qun
Shi, Fanzhe
He, Fei
Yu, Hui
Qiu, Jiaxuan
author_facet Xue, Danfeng
Pan, Shu-Ting
Zhou, Xiongming
Ye, Fangfei
Zhou, Qun
Shi, Fanzhe
He, Fei
Yu, Hui
Qiu, Jiaxuan
author_sort Xue, Danfeng
collection PubMed
description Cisplatin is widely used in the treatment of tongue squamous cell carcinoma (TSCC), but its clinical efficacy is limited by drug resistance and toxic side effects. Hence, a novel compound capable of enhancing the anticancer effect of cisplatin while reducing the side effects is urgently needed. We have previously shown that plumbagin (PLB), an anticancer phytochemical, is able to inhibit the growth of TSCC in vitro and in vivo. The objective of this study was to investigate the effect of PLB in reversing the resistance of TSCC to cisplatin as well as its molecular mechanisms. Here, we found that PLB enhances cisplatin-induced cytotoxicity, apoptosis, and autophagy in CAL27 and cisplatin-resistant CAL27/CDDP cells. PLB could inhibit the viability and growth of TSCC cells by increasing the production of intracellular reactive oxygen species (ROS). In addition, the combination treatment of PLB and cisplatin resulted in a synergistic inhibition of TSCC viability, apoptosis, and autophagy by increasing intracellular ROS, which may be achieved by activating JNK and inhibiting AKT/mTOR signaling pathways. Finally, the synergistic treatment was also demonstrated in vivo. Therefore, PLB combined with cisplatin is a potential therapeutic strategy against therapy TSCC cisplatin resistance.
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spelling pubmed-71367842020-04-18 Plumbagin Enhances the Anticancer Efficacy of Cisplatin by Increasing Intracellular ROS in Human Tongue Squamous Cell Carcinoma Xue, Danfeng Pan, Shu-Ting Zhou, Xiongming Ye, Fangfei Zhou, Qun Shi, Fanzhe He, Fei Yu, Hui Qiu, Jiaxuan Oxid Med Cell Longev Research Article Cisplatin is widely used in the treatment of tongue squamous cell carcinoma (TSCC), but its clinical efficacy is limited by drug resistance and toxic side effects. Hence, a novel compound capable of enhancing the anticancer effect of cisplatin while reducing the side effects is urgently needed. We have previously shown that plumbagin (PLB), an anticancer phytochemical, is able to inhibit the growth of TSCC in vitro and in vivo. The objective of this study was to investigate the effect of PLB in reversing the resistance of TSCC to cisplatin as well as its molecular mechanisms. Here, we found that PLB enhances cisplatin-induced cytotoxicity, apoptosis, and autophagy in CAL27 and cisplatin-resistant CAL27/CDDP cells. PLB could inhibit the viability and growth of TSCC cells by increasing the production of intracellular reactive oxygen species (ROS). In addition, the combination treatment of PLB and cisplatin resulted in a synergistic inhibition of TSCC viability, apoptosis, and autophagy by increasing intracellular ROS, which may be achieved by activating JNK and inhibiting AKT/mTOR signaling pathways. Finally, the synergistic treatment was also demonstrated in vivo. Therefore, PLB combined with cisplatin is a potential therapeutic strategy against therapy TSCC cisplatin resistance. Hindawi 2020-03-25 /pmc/articles/PMC7136784/ /pubmed/32308804 http://dx.doi.org/10.1155/2020/5649174 Text en Copyright © 2020 Danfeng Xue et al. http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Xue, Danfeng
Pan, Shu-Ting
Zhou, Xiongming
Ye, Fangfei
Zhou, Qun
Shi, Fanzhe
He, Fei
Yu, Hui
Qiu, Jiaxuan
Plumbagin Enhances the Anticancer Efficacy of Cisplatin by Increasing Intracellular ROS in Human Tongue Squamous Cell Carcinoma
title Plumbagin Enhances the Anticancer Efficacy of Cisplatin by Increasing Intracellular ROS in Human Tongue Squamous Cell Carcinoma
title_full Plumbagin Enhances the Anticancer Efficacy of Cisplatin by Increasing Intracellular ROS in Human Tongue Squamous Cell Carcinoma
title_fullStr Plumbagin Enhances the Anticancer Efficacy of Cisplatin by Increasing Intracellular ROS in Human Tongue Squamous Cell Carcinoma
title_full_unstemmed Plumbagin Enhances the Anticancer Efficacy of Cisplatin by Increasing Intracellular ROS in Human Tongue Squamous Cell Carcinoma
title_short Plumbagin Enhances the Anticancer Efficacy of Cisplatin by Increasing Intracellular ROS in Human Tongue Squamous Cell Carcinoma
title_sort plumbagin enhances the anticancer efficacy of cisplatin by increasing intracellular ros in human tongue squamous cell carcinoma
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7136784/
https://www.ncbi.nlm.nih.gov/pubmed/32308804
http://dx.doi.org/10.1155/2020/5649174
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