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Polyphyllin II inhibits liver cancer cell proliferation, migration and invasion through downregulated cofilin activity and the AKT/NF-κB pathway

The morbidity and mortality of primary liver cancer is one of the highest amongst all cancers. Deficiency of effective treatment and characteristics of cancer metastasis are believed to be responsible for this situation, thus a great demand is required for new agent development. Polyphyllin II (PP2)...

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Autores principales: Pang, Dejiang, Yang, Chengcheng, Li, Chao, Zou, Yuanfeng, Feng, Bin, Li, Lixia, Liu, Wentao, Luo, Qihui, Chen, Zhengli, Huang, Chao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Company of Biologists Ltd 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7044461/
https://www.ncbi.nlm.nih.gov/pubmed/31988091
http://dx.doi.org/10.1242/bio.046854
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author Pang, Dejiang
Yang, Chengcheng
Li, Chao
Zou, Yuanfeng
Feng, Bin
Li, Lixia
Liu, Wentao
Luo, Qihui
Chen, Zhengli
Huang, Chao
author_facet Pang, Dejiang
Yang, Chengcheng
Li, Chao
Zou, Yuanfeng
Feng, Bin
Li, Lixia
Liu, Wentao
Luo, Qihui
Chen, Zhengli
Huang, Chao
author_sort Pang, Dejiang
collection PubMed
description The morbidity and mortality of primary liver cancer is one of the highest amongst all cancers. Deficiency of effective treatment and characteristics of cancer metastasis are believed to be responsible for this situation, thus a great demand is required for new agent development. Polyphyllin II (PP2), an important steroidal saponin extracted from Rhizoma Paris, has emerged as a potential anti-cancer agent, but the effects of PP2 in liver cancers and its underlying mechanisms remain unexplored. In our study, we found that PP2 could remarkably suppress the proliferation of two liver cancer cell lines, HepG2 and BEL7402, resulting in significant cell death. Besides, low doses of PP2 have displayed properties that inhibit cellular motility and invasion of liver cancer cells. In addition, we have found that PP2-mediated cofilin activity suppression was implicated in the inhibition of liver cancer cell motility. Decreased expression of two major hydrolytic enzymes (MMP2/MMP9), through the AKT/NF-κB signaling pathway may also be also responsible for this process. Rescue experiments done with either non-phosphorylatable mutant cofilin-1 (S3A) transfection or an activator of the AKT pathway significantly reversed the inhibition effects of PP2 on liver cancer cells. Taken together, we report a potential agent for liver cancer treatment and reveal its underlying mechanisms.
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spelling pubmed-70444612020-02-27 Polyphyllin II inhibits liver cancer cell proliferation, migration and invasion through downregulated cofilin activity and the AKT/NF-κB pathway Pang, Dejiang Yang, Chengcheng Li, Chao Zou, Yuanfeng Feng, Bin Li, Lixia Liu, Wentao Luo, Qihui Chen, Zhengli Huang, Chao Biol Open Research Article The morbidity and mortality of primary liver cancer is one of the highest amongst all cancers. Deficiency of effective treatment and characteristics of cancer metastasis are believed to be responsible for this situation, thus a great demand is required for new agent development. Polyphyllin II (PP2), an important steroidal saponin extracted from Rhizoma Paris, has emerged as a potential anti-cancer agent, but the effects of PP2 in liver cancers and its underlying mechanisms remain unexplored. In our study, we found that PP2 could remarkably suppress the proliferation of two liver cancer cell lines, HepG2 and BEL7402, resulting in significant cell death. Besides, low doses of PP2 have displayed properties that inhibit cellular motility and invasion of liver cancer cells. In addition, we have found that PP2-mediated cofilin activity suppression was implicated in the inhibition of liver cancer cell motility. Decreased expression of two major hydrolytic enzymes (MMP2/MMP9), through the AKT/NF-κB signaling pathway may also be also responsible for this process. Rescue experiments done with either non-phosphorylatable mutant cofilin-1 (S3A) transfection or an activator of the AKT pathway significantly reversed the inhibition effects of PP2 on liver cancer cells. Taken together, we report a potential agent for liver cancer treatment and reveal its underlying mechanisms. The Company of Biologists Ltd 2020-02-07 /pmc/articles/PMC7044461/ /pubmed/31988091 http://dx.doi.org/10.1242/bio.046854 Text en © 2020. Published by The Company of Biologists Ltd http://creativecommons.org/licenses/by/4.0This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
spellingShingle Research Article
Pang, Dejiang
Yang, Chengcheng
Li, Chao
Zou, Yuanfeng
Feng, Bin
Li, Lixia
Liu, Wentao
Luo, Qihui
Chen, Zhengli
Huang, Chao
Polyphyllin II inhibits liver cancer cell proliferation, migration and invasion through downregulated cofilin activity and the AKT/NF-κB pathway
title Polyphyllin II inhibits liver cancer cell proliferation, migration and invasion through downregulated cofilin activity and the AKT/NF-κB pathway
title_full Polyphyllin II inhibits liver cancer cell proliferation, migration and invasion through downregulated cofilin activity and the AKT/NF-κB pathway
title_fullStr Polyphyllin II inhibits liver cancer cell proliferation, migration and invasion through downregulated cofilin activity and the AKT/NF-κB pathway
title_full_unstemmed Polyphyllin II inhibits liver cancer cell proliferation, migration and invasion through downregulated cofilin activity and the AKT/NF-κB pathway
title_short Polyphyllin II inhibits liver cancer cell proliferation, migration and invasion through downregulated cofilin activity and the AKT/NF-κB pathway
title_sort polyphyllin ii inhibits liver cancer cell proliferation, migration and invasion through downregulated cofilin activity and the akt/nf-κb pathway
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7044461/
https://www.ncbi.nlm.nih.gov/pubmed/31988091
http://dx.doi.org/10.1242/bio.046854
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