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Inhibition on Proteasome β1 Subunit Might Contribute to the Anti-Cancer Effects of Fangchinoline in Human Prostate Cancer Cells

Fangchinoline is a bisbenzylisoquinoline alkaloid isolated from Radix Stephaniae tetrandrae S. Moore. Fangchinoline and its structure analogue, tetrandrine, exhibited direct binding affinity with recombinant human proteasome β1 subunit and also inhibited its activity in vitro. In cultured prostate P...

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Autores principales: Li, Dong, Lu, Yu, Sun, Peng, Feng, Li-Xing, Liu, Miao, Hu, Li-Hong, Wu, Wan-Ying, Jiang, Bao-Hong, Yang, Min, Qu, Xiao-Bo, Guo, De-An, Liu, Xuan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4626104/
https://www.ncbi.nlm.nih.gov/pubmed/26512898
http://dx.doi.org/10.1371/journal.pone.0141681
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author Li, Dong
Lu, Yu
Sun, Peng
Feng, Li-Xing
Liu, Miao
Hu, Li-Hong
Wu, Wan-Ying
Jiang, Bao-Hong
Yang, Min
Qu, Xiao-Bo
Guo, De-An
Liu, Xuan
author_facet Li, Dong
Lu, Yu
Sun, Peng
Feng, Li-Xing
Liu, Miao
Hu, Li-Hong
Wu, Wan-Ying
Jiang, Bao-Hong
Yang, Min
Qu, Xiao-Bo
Guo, De-An
Liu, Xuan
author_sort Li, Dong
collection PubMed
description Fangchinoline is a bisbenzylisoquinoline alkaloid isolated from Radix Stephaniae tetrandrae S. Moore. Fangchinoline and its structure analogue, tetrandrine, exhibited direct binding affinity with recombinant human proteasome β1 subunit and also inhibited its activity in vitro. In cultured prostate PC-3 cells and LnCap cells, fangchinoline could dose-dependently inhibit cell proliferation and caspase-like activity of cellular proteasome which was mediated by proteasome β1 subunit. The inhibitive effect of fangchinoline on caspase-like activity of proteasome was also observed in purified human erythrocyte 20S proteasome. In PC-3 cells, fangchinoline induced cell cycle arrest at G0/G1 phase and apoptosis. Treatment of PC-3 tumor-bearing nude mice with fangchinoline inhibited tumor growth, induced apoptosis and also caused decrease in proteasome activities in tumor xenografts. Dose-dependent and time-dependent accumulation of ubiquitinated proteins and important proteasome substrates such as p27, Bax and IκB-α were observed in fangchinoline-treated cells. Over-expression of proteasome β1 subunit by plasmid transfection increased sensitivity of cells to the cytotoxicity of fangchinoline while knockdown of proteasome β1 subunit ameliorated cytotoxicity of fangchinoline in PC-3 cells. Results of the present study suggested that proteasome inhibition was involved in the anti-cancer effects of fangchinoline. Fangchinoline and its structure analogues might be new natural proteasome inhibitors targeting β1 subunit.
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spelling pubmed-46261042015-11-06 Inhibition on Proteasome β1 Subunit Might Contribute to the Anti-Cancer Effects of Fangchinoline in Human Prostate Cancer Cells Li, Dong Lu, Yu Sun, Peng Feng, Li-Xing Liu, Miao Hu, Li-Hong Wu, Wan-Ying Jiang, Bao-Hong Yang, Min Qu, Xiao-Bo Guo, De-An Liu, Xuan PLoS One Research Article Fangchinoline is a bisbenzylisoquinoline alkaloid isolated from Radix Stephaniae tetrandrae S. Moore. Fangchinoline and its structure analogue, tetrandrine, exhibited direct binding affinity with recombinant human proteasome β1 subunit and also inhibited its activity in vitro. In cultured prostate PC-3 cells and LnCap cells, fangchinoline could dose-dependently inhibit cell proliferation and caspase-like activity of cellular proteasome which was mediated by proteasome β1 subunit. The inhibitive effect of fangchinoline on caspase-like activity of proteasome was also observed in purified human erythrocyte 20S proteasome. In PC-3 cells, fangchinoline induced cell cycle arrest at G0/G1 phase and apoptosis. Treatment of PC-3 tumor-bearing nude mice with fangchinoline inhibited tumor growth, induced apoptosis and also caused decrease in proteasome activities in tumor xenografts. Dose-dependent and time-dependent accumulation of ubiquitinated proteins and important proteasome substrates such as p27, Bax and IκB-α were observed in fangchinoline-treated cells. Over-expression of proteasome β1 subunit by plasmid transfection increased sensitivity of cells to the cytotoxicity of fangchinoline while knockdown of proteasome β1 subunit ameliorated cytotoxicity of fangchinoline in PC-3 cells. Results of the present study suggested that proteasome inhibition was involved in the anti-cancer effects of fangchinoline. Fangchinoline and its structure analogues might be new natural proteasome inhibitors targeting β1 subunit. Public Library of Science 2015-10-29 /pmc/articles/PMC4626104/ /pubmed/26512898 http://dx.doi.org/10.1371/journal.pone.0141681 Text en © 2015 Li et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Li, Dong
Lu, Yu
Sun, Peng
Feng, Li-Xing
Liu, Miao
Hu, Li-Hong
Wu, Wan-Ying
Jiang, Bao-Hong
Yang, Min
Qu, Xiao-Bo
Guo, De-An
Liu, Xuan
Inhibition on Proteasome β1 Subunit Might Contribute to the Anti-Cancer Effects of Fangchinoline in Human Prostate Cancer Cells
title Inhibition on Proteasome β1 Subunit Might Contribute to the Anti-Cancer Effects of Fangchinoline in Human Prostate Cancer Cells
title_full Inhibition on Proteasome β1 Subunit Might Contribute to the Anti-Cancer Effects of Fangchinoline in Human Prostate Cancer Cells
title_fullStr Inhibition on Proteasome β1 Subunit Might Contribute to the Anti-Cancer Effects of Fangchinoline in Human Prostate Cancer Cells
title_full_unstemmed Inhibition on Proteasome β1 Subunit Might Contribute to the Anti-Cancer Effects of Fangchinoline in Human Prostate Cancer Cells
title_short Inhibition on Proteasome β1 Subunit Might Contribute to the Anti-Cancer Effects of Fangchinoline in Human Prostate Cancer Cells
title_sort inhibition on proteasome β1 subunit might contribute to the anti-cancer effects of fangchinoline in human prostate cancer cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4626104/
https://www.ncbi.nlm.nih.gov/pubmed/26512898
http://dx.doi.org/10.1371/journal.pone.0141681
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