Cargando…

Phenolic alkaloids from Menispermum dauricum inhibits BxPC-3 pancreatic cancer cells by blocking of Hedgehog signaling pathway

BACKGROUND: The Hedgehog (Hh) signaling pathway plays an important role in pancreatic cancer (PC) cells. Phenolic alkaloids from Menispermum dauricum (PAMD), a traditional Chinese medicine used for the treatment of immune disorders, have been reported to have antitumor activity recently. OBJECTIVE:...

Descripción completa

Detalles Bibliográficos
Autores principales: Zhou, Zhong-guang, Zhang, Chao-ying, Fei, Hong-xin, Zhong, Li-li, Bai, Yun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Medknow Publications & Media Pvt Ltd 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4621636/
https://www.ncbi.nlm.nih.gov/pubmed/26600712
http://dx.doi.org/10.4103/0973-1296.165548
_version_ 1782397467395883008
author Zhou, Zhong-guang
Zhang, Chao-ying
Fei, Hong-xin
Zhong, Li-li
Bai, Yun
author_facet Zhou, Zhong-guang
Zhang, Chao-ying
Fei, Hong-xin
Zhong, Li-li
Bai, Yun
author_sort Zhou, Zhong-guang
collection PubMed
description BACKGROUND: The Hedgehog (Hh) signaling pathway plays an important role in pancreatic cancer (PC) cells. Phenolic alkaloids from Menispermum dauricum (PAMD), a traditional Chinese medicine used for the treatment of immune disorders, have been reported to have antitumor activity recently. OBJECTIVE: To investigate the efficacy and mechanism of PAMD against PC cell BxPC-3. MATERIALS AND METHODS: F assay was used to assess cell proliferation inhibition of PAMD; the apoptotic induction and cell cycle arrest was detected by flow cytometry; the BxPC-3 xenograft was established to evaluate the tumor growth inhibition of PAMD; hematoxylin-eosin staining was applied to analyze the pathological morphology of tumor tissues; immunohistochemistry (IHC) and Western blot was adopted to detect the protein levels; quantitative real-time polymerase chain reaction was used to determine the mRNA expressions. RESULTS: PAMD shows time-and dose-dependent proliferation inhibition on the BxPC-3 cell, induced G0/G1 phase arrest and cell apoptosis in vitro. PAMD also showed better inhibition of tumor growth and a preferable safety profile compared with chemotherapeutic regimen 5-fluoro-2, 4 (1 H, 3 H) pyrimidinedione in BxPC-3 xenograft in vivo. Furthermore, PAMD directly decreases the protein and mRNA levels of Sonic Hedgehog (Shh) and its downstream transcription factor Gli-1 in the BxPC-3 tumor tissues. CONCLUSION: The treatment of PAMD displayed Hh signaling pathway blockade through decreasing the protein and mRNA levels of Shh and its downstream transcription factor Gli-1, suggesting a promising strategy in treating human PC.
format Online
Article
Text
id pubmed-4621636
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher Medknow Publications & Media Pvt Ltd
record_format MEDLINE/PubMed
spelling pubmed-46216362015-11-23 Phenolic alkaloids from Menispermum dauricum inhibits BxPC-3 pancreatic cancer cells by blocking of Hedgehog signaling pathway Zhou, Zhong-guang Zhang, Chao-ying Fei, Hong-xin Zhong, Li-li Bai, Yun Pharmacogn Mag Original Article BACKGROUND: The Hedgehog (Hh) signaling pathway plays an important role in pancreatic cancer (PC) cells. Phenolic alkaloids from Menispermum dauricum (PAMD), a traditional Chinese medicine used for the treatment of immune disorders, have been reported to have antitumor activity recently. OBJECTIVE: To investigate the efficacy and mechanism of PAMD against PC cell BxPC-3. MATERIALS AND METHODS: F assay was used to assess cell proliferation inhibition of PAMD; the apoptotic induction and cell cycle arrest was detected by flow cytometry; the BxPC-3 xenograft was established to evaluate the tumor growth inhibition of PAMD; hematoxylin-eosin staining was applied to analyze the pathological morphology of tumor tissues; immunohistochemistry (IHC) and Western blot was adopted to detect the protein levels; quantitative real-time polymerase chain reaction was used to determine the mRNA expressions. RESULTS: PAMD shows time-and dose-dependent proliferation inhibition on the BxPC-3 cell, induced G0/G1 phase arrest and cell apoptosis in vitro. PAMD also showed better inhibition of tumor growth and a preferable safety profile compared with chemotherapeutic regimen 5-fluoro-2, 4 (1 H, 3 H) pyrimidinedione in BxPC-3 xenograft in vivo. Furthermore, PAMD directly decreases the protein and mRNA levels of Sonic Hedgehog (Shh) and its downstream transcription factor Gli-1 in the BxPC-3 tumor tissues. CONCLUSION: The treatment of PAMD displayed Hh signaling pathway blockade through decreasing the protein and mRNA levels of Shh and its downstream transcription factor Gli-1, suggesting a promising strategy in treating human PC. Medknow Publications & Media Pvt Ltd 2015 /pmc/articles/PMC4621636/ /pubmed/26600712 http://dx.doi.org/10.4103/0973-1296.165548 Text en Copyright: © Pharmacognosy Magazine http://creativecommons.org/licenses/by-nc-sa/3.0 This is an open access article distributed under the terms of the Creative Commons Attribution NonCommercial ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non commercially, as long as the author is credited and the new creations are licensed under the identical terms.
spellingShingle Original Article
Zhou, Zhong-guang
Zhang, Chao-ying
Fei, Hong-xin
Zhong, Li-li
Bai, Yun
Phenolic alkaloids from Menispermum dauricum inhibits BxPC-3 pancreatic cancer cells by blocking of Hedgehog signaling pathway
title Phenolic alkaloids from Menispermum dauricum inhibits BxPC-3 pancreatic cancer cells by blocking of Hedgehog signaling pathway
title_full Phenolic alkaloids from Menispermum dauricum inhibits BxPC-3 pancreatic cancer cells by blocking of Hedgehog signaling pathway
title_fullStr Phenolic alkaloids from Menispermum dauricum inhibits BxPC-3 pancreatic cancer cells by blocking of Hedgehog signaling pathway
title_full_unstemmed Phenolic alkaloids from Menispermum dauricum inhibits BxPC-3 pancreatic cancer cells by blocking of Hedgehog signaling pathway
title_short Phenolic alkaloids from Menispermum dauricum inhibits BxPC-3 pancreatic cancer cells by blocking of Hedgehog signaling pathway
title_sort phenolic alkaloids from menispermum dauricum inhibits bxpc-3 pancreatic cancer cells by blocking of hedgehog signaling pathway
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4621636/
https://www.ncbi.nlm.nih.gov/pubmed/26600712
http://dx.doi.org/10.4103/0973-1296.165548
work_keys_str_mv AT zhouzhongguang phenolicalkaloidsfrommenispermumdauricuminhibitsbxpc3pancreaticcancercellsbyblockingofhedgehogsignalingpathway
AT zhangchaoying phenolicalkaloidsfrommenispermumdauricuminhibitsbxpc3pancreaticcancercellsbyblockingofhedgehogsignalingpathway
AT feihongxin phenolicalkaloidsfrommenispermumdauricuminhibitsbxpc3pancreaticcancercellsbyblockingofhedgehogsignalingpathway
AT zhonglili phenolicalkaloidsfrommenispermumdauricuminhibitsbxpc3pancreaticcancercellsbyblockingofhedgehogsignalingpathway
AT baiyun phenolicalkaloidsfrommenispermumdauricuminhibitsbxpc3pancreaticcancercellsbyblockingofhedgehogsignalingpathway