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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Frontiers Media S.A.
2021-04-01
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Series: | Frontiers in Pharmacology |
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Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2021.600296/full |
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doaj-dff2561993bb42b081ebaf5d5c05073e |
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Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Chenyang Xue Wei Chen Aiwu Yuan Cheng Chen Shuaihu Li Kai Chen Yang Zhao Tian Xiao Genze Shao Yongdong Zou Duo Zheng |
spellingShingle |
Chenyang Xue Wei Chen Aiwu Yuan Cheng Chen Shuaihu Li Kai Chen Yang Zhao Tian Xiao Genze Shao Yongdong Zou Duo Zheng Dezocine, An Opioid Analgesic, Exerts Antitumor Effects in Triple-Negative Breast Cancer by Targeting Nicotinamide Phosphoribosyltransferase Frontiers in Pharmacology triple-negative breast cancer dezocine opioid NAMPT proliferation metastasis |
author_facet |
Chenyang Xue Wei Chen Aiwu Yuan Cheng Chen Shuaihu Li Kai Chen Yang Zhao Tian Xiao Genze Shao Yongdong Zou Duo Zheng |
author_sort |
Chenyang Xue |
title |
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_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_sort |
dezocine, an opioid analgesic, exerts antitumor effects in triple-negative breast cancer by targeting nicotinamide phosphoribosyltransferase |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Pharmacology |
issn |
1663-9812 |
publishDate |
2021-04-01 |
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. |
topic |
triple-negative breast cancer dezocine opioid NAMPT proliferation metastasis |
url |
https://www.frontiersin.org/articles/10.3389/fphar.2021.600296/full |
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doaj-dff2561993bb42b081ebaf5d5c05073e2021-04-12T08:32:32ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122021-04-011210.3389/fphar.2021.600296600296Dezocine, An Opioid Analgesic, Exerts Antitumor Effects in Triple-Negative Breast Cancer by Targeting Nicotinamide PhosphoribosyltransferaseChenyang Xue0Wei Chen1Aiwu Yuan2Cheng Chen3Shuaihu Li4Kai Chen5Yang Zhao6Tian Xiao7Genze Shao8Yongdong Zou9Duo Zheng10Guangdong Provincial Key Laboratory of Regional Immunity and Diseases, Shenzhen University International Cancer Center, Department of Cell Biology and Genetics, School of Medicine, School of Pharmaceutical Sciences, Health Science Center, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen, ChinaGuangdong Provincial Key Laboratory of Regional Immunity and Diseases, Shenzhen University International Cancer Center, Department of Cell Biology and Genetics, School of Medicine, School of Pharmaceutical Sciences, Health Science Center, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen, ChinaDepartment of Anesthesiology, Longgang District Maternity & Child Healthcare Hospital of Shenzhen City, Shenzhen, ChinaGuangdong Provincial Key Laboratory of Regional Immunity and Diseases, Shenzhen University International Cancer Center, Department of Cell Biology and Genetics, School of Medicine, School of Pharmaceutical Sciences, Health Science Center, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen, ChinaGuangdong Provincial Key Laboratory of Regional Immunity and Diseases, Shenzhen University International Cancer Center, Department of Cell Biology and Genetics, School of Medicine, School of Pharmaceutical Sciences, Health Science Center, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen, ChinaCollege of Chemistry and Chemical Engineering, Central South University, Changsha, ChinaDepartment of Anesthesiology, Longgang District Maternity & Child Healthcare Hospital of Shenzhen City, Shenzhen, ChinaGuangdong Provincial Key Laboratory of Regional Immunity and Diseases, Shenzhen University International Cancer Center, Department of Cell Biology and Genetics, School of Medicine, School of Pharmaceutical Sciences, Health Science Center, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen, ChinaDepartment of Cell Biology, School of Basic Medical Sciences, Peking University, Beijing, ChinaGuangdong Provincial Key Laboratory of Regional Immunity and Diseases, Shenzhen University International Cancer Center, Department of Cell Biology and Genetics, School of Medicine, School of Pharmaceutical Sciences, Health Science Center, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen, ChinaGuangdong Provincial Key Laboratory of Regional Immunity and Diseases, Shenzhen University International Cancer Center, Department of Cell Biology and Genetics, School of Medicine, School of Pharmaceutical Sciences, Health Science Center, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen, ChinaOpioids 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.https://www.frontiersin.org/articles/10.3389/fphar.2021.600296/fulltriple-negative breast cancerdezocineopioidNAMPTproliferationmetastasis |