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Dezocine, An Opioid Analgesic, Exerts Antitumor Effects in Triple-Negative Breast Cancer by Targeting Nicotinamide Phosphoribosyltransferase

Opioids are a potential adjuvant treatment for certain cancers; while they are primarily used to relieve chronic pain, these drugs may also affect cancer progression and recurrence. Dezocine is one opioid commonly used in China, but its effects on cancer cells are unknown. Here, we demonstrated the...

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Autores principales: Xue, Chenyang, Chen, Wei, Yuan, Aiwu, Chen, Cheng, Li, Shuaihu, Chen, Kai, Zhao, Yang, Xiao, Tian, Shao, Genze, Zou, Yongdong, Zheng, Duo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8072669/
https://www.ncbi.nlm.nih.gov/pubmed/33912035
http://dx.doi.org/10.3389/fphar.2021.600296
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author Xue, Chenyang
Chen, Wei
Yuan, Aiwu
Chen, Cheng
Li, Shuaihu
Chen, Kai
Zhao, Yang
Xiao, Tian
Shao, Genze
Zou, Yongdong
Zheng, Duo
author_facet Xue, Chenyang
Chen, Wei
Yuan, Aiwu
Chen, Cheng
Li, Shuaihu
Chen, Kai
Zhao, Yang
Xiao, Tian
Shao, Genze
Zou, Yongdong
Zheng, Duo
author_sort Xue, Chenyang
collection PubMed
description Opioids are a potential adjuvant treatment for certain cancers; while they are primarily used to relieve chronic pain, these drugs may also affect cancer progression and recurrence. Dezocine is one opioid commonly used in China, but its effects on cancer cells are unknown. Here, we demonstrated the inhibitory effect of dezocine on triple-negative breast cancer (TNBC) cells, and determined the underlying molecular mechanism. We found that dezocine suppressed cell proliferation, migration and invasion, and induced apoptosis in TNBC cells. Xenograft models demonstrated the inhibitory effects of dezocine treatment on TNBC tumor growth in vivo. The anticancer effects of dezocine were independent of opioid receptors, which are not highly expressed by normal breast or breast cancer tissues. A pull-down assay and LC-MS/MS analysis indicated that dezocine directly targets NAMPT: computer modeling verified that the free energy of dezocine kinetically bound into the pocket of NAMPT was −17.4 kcal/mol. Consequently, dezocine treatment inhibited NAMPT enzyme activity, resulting in cellular NAD abolishment. We confirmed the dezocine-induced inhibition of cell proliferation by both NAMPT knockdown and upon treatment with the inhibitor FK866. Our results suggest that both dezocine and NAMPT might represent novel therapeutic targets for TNBC.
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spelling pubmed-80726692021-04-27 Dezocine, An Opioid Analgesic, Exerts Antitumor Effects in Triple-Negative Breast Cancer by Targeting Nicotinamide Phosphoribosyltransferase Xue, Chenyang Chen, Wei Yuan, Aiwu Chen, Cheng Li, Shuaihu Chen, Kai Zhao, Yang Xiao, Tian Shao, Genze Zou, Yongdong Zheng, Duo Front Pharmacol Pharmacology Opioids are a potential adjuvant treatment for certain cancers; while they are primarily used to relieve chronic pain, these drugs may also affect cancer progression and recurrence. Dezocine is one opioid commonly used in China, but its effects on cancer cells are unknown. Here, we demonstrated the inhibitory effect of dezocine on triple-negative breast cancer (TNBC) cells, and determined the underlying molecular mechanism. We found that dezocine suppressed cell proliferation, migration and invasion, and induced apoptosis in TNBC cells. Xenograft models demonstrated the inhibitory effects of dezocine treatment on TNBC tumor growth in vivo. The anticancer effects of dezocine were independent of opioid receptors, which are not highly expressed by normal breast or breast cancer tissues. A pull-down assay and LC-MS/MS analysis indicated that dezocine directly targets NAMPT: computer modeling verified that the free energy of dezocine kinetically bound into the pocket of NAMPT was −17.4 kcal/mol. Consequently, dezocine treatment inhibited NAMPT enzyme activity, resulting in cellular NAD abolishment. We confirmed the dezocine-induced inhibition of cell proliferation by both NAMPT knockdown and upon treatment with the inhibitor FK866. Our results suggest that both dezocine and NAMPT might represent novel therapeutic targets for TNBC. Frontiers Media S.A. 2021-04-12 /pmc/articles/PMC8072669/ /pubmed/33912035 http://dx.doi.org/10.3389/fphar.2021.600296 Text en Copyright © 2021 Xue, Chen, Yuan, Chen, Li, Chen, Zhao, Xiao, Shao, Zou and Zheng. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Xue, Chenyang
Chen, Wei
Yuan, Aiwu
Chen, Cheng
Li, Shuaihu
Chen, Kai
Zhao, Yang
Xiao, Tian
Shao, Genze
Zou, Yongdong
Zheng, Duo
Dezocine, An Opioid Analgesic, Exerts Antitumor Effects in Triple-Negative Breast Cancer by Targeting Nicotinamide Phosphoribosyltransferase
title Dezocine, An Opioid Analgesic, Exerts Antitumor Effects in Triple-Negative Breast Cancer by Targeting Nicotinamide Phosphoribosyltransferase
title_full Dezocine, An Opioid Analgesic, Exerts Antitumor Effects in Triple-Negative Breast Cancer by Targeting Nicotinamide Phosphoribosyltransferase
title_fullStr Dezocine, An Opioid Analgesic, Exerts Antitumor Effects in Triple-Negative Breast Cancer by Targeting Nicotinamide Phosphoribosyltransferase
title_full_unstemmed Dezocine, An Opioid Analgesic, Exerts Antitumor Effects in Triple-Negative Breast Cancer by Targeting Nicotinamide Phosphoribosyltransferase
title_short Dezocine, An Opioid Analgesic, Exerts Antitumor Effects in Triple-Negative Breast Cancer by Targeting Nicotinamide Phosphoribosyltransferase
title_sort dezocine, an opioid analgesic, exerts antitumor effects in triple-negative breast cancer by targeting nicotinamide phosphoribosyltransferase
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8072669/
https://www.ncbi.nlm.nih.gov/pubmed/33912035
http://dx.doi.org/10.3389/fphar.2021.600296
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