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Norcantharidin inhibits proliferation and promotes apoptosis via c‐Met/Akt/mTOR pathway in human osteosarcoma cells

Osteosarcoma (OS) is the most common malignant bone tumor and frequently affects adolescents. Norcantharidin (NCTD), a demethylated derivative of cantharidin, has been reported to exhibit anticancer activity against various types of tumors but not human OS. The aim of the present study was to evalua...

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Autores principales: Mei, Liangwei, Sang, Wenhua, Cui, Kai, Zhang, Yabin, Chen, Fuchun, Li, Xiaochun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6361574/
https://www.ncbi.nlm.nih.gov/pubmed/30520540
http://dx.doi.org/10.1111/cas.13900
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author Mei, Liangwei
Sang, Wenhua
Cui, Kai
Zhang, Yabin
Chen, Fuchun
Li, Xiaochun
author_facet Mei, Liangwei
Sang, Wenhua
Cui, Kai
Zhang, Yabin
Chen, Fuchun
Li, Xiaochun
author_sort Mei, Liangwei
collection PubMed
description Osteosarcoma (OS) is the most common malignant bone tumor and frequently affects adolescents. Norcantharidin (NCTD), a demethylated derivative of cantharidin, has been reported to exhibit anticancer activity against various types of tumors but not human OS. The aim of the present study was to evaluate the effects of NCTD on OS cell lines (MG63 and HOS) and to explore the underlying mechanisms. In the present study, the proliferation of OS cells decreased significantly, while the apoptosis was accelerated significantly after exposure to NCTD. Meanwhile, our results also indicated that NCTD could suppress the migration and invasion, decrease the colony‐forming ability and induce S phase cell cycle arrest of OS cells in a dose‐dependent manner. Moreover, our results revealed that the anticancer effects induced by NCTD on OS cells involved autophagy, mitophagy, endoplasmic reticulum stress and c‐Met pathway. Furthermore, the results of animal experiments showed that NCTD inhibited tumor growth in a xenograft model of human OS. These results provide important new insight into the possible molecular mechanisms of NCTD and highlight its potential use as an antitumor drug for human OS.
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spelling pubmed-63615742019-02-14 Norcantharidin inhibits proliferation and promotes apoptosis via c‐Met/Akt/mTOR pathway in human osteosarcoma cells Mei, Liangwei Sang, Wenhua Cui, Kai Zhang, Yabin Chen, Fuchun Li, Xiaochun Cancer Sci Original Articles Osteosarcoma (OS) is the most common malignant bone tumor and frequently affects adolescents. Norcantharidin (NCTD), a demethylated derivative of cantharidin, has been reported to exhibit anticancer activity against various types of tumors but not human OS. The aim of the present study was to evaluate the effects of NCTD on OS cell lines (MG63 and HOS) and to explore the underlying mechanisms. In the present study, the proliferation of OS cells decreased significantly, while the apoptosis was accelerated significantly after exposure to NCTD. Meanwhile, our results also indicated that NCTD could suppress the migration and invasion, decrease the colony‐forming ability and induce S phase cell cycle arrest of OS cells in a dose‐dependent manner. Moreover, our results revealed that the anticancer effects induced by NCTD on OS cells involved autophagy, mitophagy, endoplasmic reticulum stress and c‐Met pathway. Furthermore, the results of animal experiments showed that NCTD inhibited tumor growth in a xenograft model of human OS. These results provide important new insight into the possible molecular mechanisms of NCTD and highlight its potential use as an antitumor drug for human OS. John Wiley and Sons Inc. 2019-01-02 2019-02 /pmc/articles/PMC6361574/ /pubmed/30520540 http://dx.doi.org/10.1111/cas.13900 Text en © 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Original Articles
Mei, Liangwei
Sang, Wenhua
Cui, Kai
Zhang, Yabin
Chen, Fuchun
Li, Xiaochun
Norcantharidin inhibits proliferation and promotes apoptosis via c‐Met/Akt/mTOR pathway in human osteosarcoma cells
title Norcantharidin inhibits proliferation and promotes apoptosis via c‐Met/Akt/mTOR pathway in human osteosarcoma cells
title_full Norcantharidin inhibits proliferation and promotes apoptosis via c‐Met/Akt/mTOR pathway in human osteosarcoma cells
title_fullStr Norcantharidin inhibits proliferation and promotes apoptosis via c‐Met/Akt/mTOR pathway in human osteosarcoma cells
title_full_unstemmed Norcantharidin inhibits proliferation and promotes apoptosis via c‐Met/Akt/mTOR pathway in human osteosarcoma cells
title_short Norcantharidin inhibits proliferation and promotes apoptosis via c‐Met/Akt/mTOR pathway in human osteosarcoma cells
title_sort norcantharidin inhibits proliferation and promotes apoptosis via c‐met/akt/mtor pathway in human osteosarcoma cells
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6361574/
https://www.ncbi.nlm.nih.gov/pubmed/30520540
http://dx.doi.org/10.1111/cas.13900
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