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Gracillin shows potent efficacy against colorectal cancer through inhibiting the STAT3 pathway

Colorectal cancer (CRC) accounts for about 10% of all annually diagnosed cancers and cancer‐related deaths worldwide. STAT3 plays a vital role in the occurrence and development of tumours. Gracillin has shown a significant antitumour activity in tumours, but its mechanism remains unknown. The human...

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Autores principales: Yang, Lehe, Zhu, Tianru, Ye, Hua, Shen, Yili, Li, Zhiping, Chen, Luye, Wang, Canwei, Chen, Xia, Zhao, Haiyang, Xiang, Youqun, Xiao, Zhongxiang, Zhao, Chengguang, Li, Jifa, Hu, Wanle
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7812262/
https://www.ncbi.nlm.nih.gov/pubmed/33259114
http://dx.doi.org/10.1111/jcmm.16134
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author Yang, Lehe
Zhu, Tianru
Ye, Hua
Shen, Yili
Li, Zhiping
Chen, Luye
Wang, Canwei
Chen, Xia
Zhao, Haiyang
Xiang, Youqun
Xiao, Zhongxiang
Zhao, Chengguang
Li, Jifa
Hu, Wanle
author_facet Yang, Lehe
Zhu, Tianru
Ye, Hua
Shen, Yili
Li, Zhiping
Chen, Luye
Wang, Canwei
Chen, Xia
Zhao, Haiyang
Xiang, Youqun
Xiao, Zhongxiang
Zhao, Chengguang
Li, Jifa
Hu, Wanle
author_sort Yang, Lehe
collection PubMed
description Colorectal cancer (CRC) accounts for about 10% of all annually diagnosed cancers and cancer‐related deaths worldwide. STAT3 plays a vital role in the occurrence and development of tumours. Gracillin has shown a significant antitumour activity in tumours, but its mechanism remains unknown. The human CRC cell lines HCT116, RKO, and SW480 and immunodeficient mice were used as models to study the effects of gracillin on cell proliferation, migration and apoptosis. These were evaluated by cell viability, colony formation, wound‐healing migration and cell apoptosis assays. Luciferase reporter assay, and immunostaining and western blot analyses were used to explore the specific mechanism through which gracillin exerts its effects. Gracillin significantly reduces viability and migration and stimulates apoptosis in human CRC cells. It also significantly inhibits tumour growth with no apparent physiological toxicity in animal model experiments. Moreover, gracillin is found to inhibit STAT3 phosphorylation and STAT3 target gene products. In addition, gracillin inhibits IL6‐induced nuclear translocation of P‐STAT3. Gracillin shows potent efficacy against CRC by inhibiting the STAT3 pathway. It should be further explored as a unique STAT3 inhibitor for the treatment of CRC.
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spelling pubmed-78122622021-01-22 Gracillin shows potent efficacy against colorectal cancer through inhibiting the STAT3 pathway Yang, Lehe Zhu, Tianru Ye, Hua Shen, Yili Li, Zhiping Chen, Luye Wang, Canwei Chen, Xia Zhao, Haiyang Xiang, Youqun Xiao, Zhongxiang Zhao, Chengguang Li, Jifa Hu, Wanle J Cell Mol Med Original Articles Colorectal cancer (CRC) accounts for about 10% of all annually diagnosed cancers and cancer‐related deaths worldwide. STAT3 plays a vital role in the occurrence and development of tumours. Gracillin has shown a significant antitumour activity in tumours, but its mechanism remains unknown. The human CRC cell lines HCT116, RKO, and SW480 and immunodeficient mice were used as models to study the effects of gracillin on cell proliferation, migration and apoptosis. These were evaluated by cell viability, colony formation, wound‐healing migration and cell apoptosis assays. Luciferase reporter assay, and immunostaining and western blot analyses were used to explore the specific mechanism through which gracillin exerts its effects. Gracillin significantly reduces viability and migration and stimulates apoptosis in human CRC cells. It also significantly inhibits tumour growth with no apparent physiological toxicity in animal model experiments. Moreover, gracillin is found to inhibit STAT3 phosphorylation and STAT3 target gene products. In addition, gracillin inhibits IL6‐induced nuclear translocation of P‐STAT3. Gracillin shows potent efficacy against CRC by inhibiting the STAT3 pathway. It should be further explored as a unique STAT3 inhibitor for the treatment of CRC. John Wiley and Sons Inc. 2020-12-01 2021-01 /pmc/articles/PMC7812262/ /pubmed/33259114 http://dx.doi.org/10.1111/jcmm.16134 Text en © 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Yang, Lehe
Zhu, Tianru
Ye, Hua
Shen, Yili
Li, Zhiping
Chen, Luye
Wang, Canwei
Chen, Xia
Zhao, Haiyang
Xiang, Youqun
Xiao, Zhongxiang
Zhao, Chengguang
Li, Jifa
Hu, Wanle
Gracillin shows potent efficacy against colorectal cancer through inhibiting the STAT3 pathway
title Gracillin shows potent efficacy against colorectal cancer through inhibiting the STAT3 pathway
title_full Gracillin shows potent efficacy against colorectal cancer through inhibiting the STAT3 pathway
title_fullStr Gracillin shows potent efficacy against colorectal cancer through inhibiting the STAT3 pathway
title_full_unstemmed Gracillin shows potent efficacy against colorectal cancer through inhibiting the STAT3 pathway
title_short Gracillin shows potent efficacy against colorectal cancer through inhibiting the STAT3 pathway
title_sort gracillin shows potent efficacy against colorectal cancer through inhibiting the stat3 pathway
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7812262/
https://www.ncbi.nlm.nih.gov/pubmed/33259114
http://dx.doi.org/10.1111/jcmm.16134
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