Saponin 1 induces apoptosis and suppresses NF-κB-mediated survival signaling in glioblastoma multiforme (GBM).

Saponin 1 is a triterpeniod saponin extracted from Anemone taipaiensis, a traditional Chinese medicine against rheumatism and phlebitis. It has also been shown to exhibit significant anti-tumor activity against human leukemia (HL-60 cells) and human hepatocellular carcinoma (Hep-G2 cells). Herein we...

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Autores principales: Juan Li, Haifeng Tang, Yun Zhang, Chi Tang, Bo Li, Yuangang Wang, Zhenhui Gao, Peng Luo, Anan Yin, Xiaoyang Wang, Guang Cheng, Zhou Fei
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Publicado: Public Library of Science (PLoS) 2013
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spelling oai:doaj.org-article:360bfc0babcd48bf8c9603898a4968b72021-11-18T08:45:09ZSaponin 1 induces apoptosis and suppresses NF-κB-mediated survival signaling in glioblastoma multiforme (GBM).1932-620310.1371/journal.pone.0081258https://doaj.org/article/360bfc0babcd48bf8c9603898a4968b72013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24278406/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Saponin 1 is a triterpeniod saponin extracted from Anemone taipaiensis, a traditional Chinese medicine against rheumatism and phlebitis. It has also been shown to exhibit significant anti-tumor activity against human leukemia (HL-60 cells) and human hepatocellular carcinoma (Hep-G2 cells). Herein we investigated the effect of saponin 1 in human glioblastoma multiforme (GBM) U251MG and U87MG cells. Saponin 1 induced significant growth inhibition in both glioblastoma cell lines, with a 50% inhibitory concentration at 24 h of 7.4 µg/ml in U251MG cells and 8.6 µg/ml in U87MG cells, respectively. Nuclear fluorescent staining and electron microscopy showed that saponin 1 caused characteristic apoptotic morphological changes in the GBM cell lines. Saponin 1-induced apoptosis was also verified by DNA ladder electrophoresis and flow cytometry. Additionally, immunocytochemistry and western blotting analyses revealed a time-dependent decrease in the expression and nuclear location of NF-κB following saponin 1 treatment. Western blotting data indicated a significant decreased expression of inhibitors of apoptosis (IAP) family members,(e.g., survivin and XIAP) by saponin 1. Moreover, saponin 1 caused a decrease in the Bcl-2/Bax ratio and initiated apoptosis by activating caspase-9 and caspase-3 in the GBM cell lines. These findings indicate that saponin 1 inhibits cell growth of GBM cells at least partially by inducing apoptosis and inhibiting survival signaling mediated by NF-κB. In addition, in vivo study also demonstrated an obvious inhibition of saponin 1 treatment on the tumor growth of U251MG and U87MG cells-produced xenograft tumors in nude mice. Given the minimal toxicities of saponin 1 in non-neoplastic astrocytes, our results suggest that saponin 1 exhibits significant in vitro and in vivo anti-tumor efficacy and merits further investigation as a potential therapeutic agent for GBM.Juan LiHaifeng TangYun ZhangChi TangBo LiYuangang WangZhenhui GaoPeng LuoAnan YinXiaoyang WangGuang ChengZhou FeiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 11, p e81258 (2013)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Juan Li
Haifeng Tang
Yun Zhang
Chi Tang
Bo Li
Yuangang Wang
Zhenhui Gao
Peng Luo
Anan Yin
Xiaoyang Wang
Guang Cheng
Zhou Fei
Saponin 1 induces apoptosis and suppresses NF-κB-mediated survival signaling in glioblastoma multiforme (GBM).
description Saponin 1 is a triterpeniod saponin extracted from Anemone taipaiensis, a traditional Chinese medicine against rheumatism and phlebitis. It has also been shown to exhibit significant anti-tumor activity against human leukemia (HL-60 cells) and human hepatocellular carcinoma (Hep-G2 cells). Herein we investigated the effect of saponin 1 in human glioblastoma multiforme (GBM) U251MG and U87MG cells. Saponin 1 induced significant growth inhibition in both glioblastoma cell lines, with a 50% inhibitory concentration at 24 h of 7.4 µg/ml in U251MG cells and 8.6 µg/ml in U87MG cells, respectively. Nuclear fluorescent staining and electron microscopy showed that saponin 1 caused characteristic apoptotic morphological changes in the GBM cell lines. Saponin 1-induced apoptosis was also verified by DNA ladder electrophoresis and flow cytometry. Additionally, immunocytochemistry and western blotting analyses revealed a time-dependent decrease in the expression and nuclear location of NF-κB following saponin 1 treatment. Western blotting data indicated a significant decreased expression of inhibitors of apoptosis (IAP) family members,(e.g., survivin and XIAP) by saponin 1. Moreover, saponin 1 caused a decrease in the Bcl-2/Bax ratio and initiated apoptosis by activating caspase-9 and caspase-3 in the GBM cell lines. These findings indicate that saponin 1 inhibits cell growth of GBM cells at least partially by inducing apoptosis and inhibiting survival signaling mediated by NF-κB. In addition, in vivo study also demonstrated an obvious inhibition of saponin 1 treatment on the tumor growth of U251MG and U87MG cells-produced xenograft tumors in nude mice. Given the minimal toxicities of saponin 1 in non-neoplastic astrocytes, our results suggest that saponin 1 exhibits significant in vitro and in vivo anti-tumor efficacy and merits further investigation as a potential therapeutic agent for GBM.
format article
author Juan Li
Haifeng Tang
Yun Zhang
Chi Tang
Bo Li
Yuangang Wang
Zhenhui Gao
Peng Luo
Anan Yin
Xiaoyang Wang
Guang Cheng
Zhou Fei
author_facet Juan Li
Haifeng Tang
Yun Zhang
Chi Tang
Bo Li
Yuangang Wang
Zhenhui Gao
Peng Luo
Anan Yin
Xiaoyang Wang
Guang Cheng
Zhou Fei
author_sort Juan Li
title Saponin 1 induces apoptosis and suppresses NF-κB-mediated survival signaling in glioblastoma multiforme (GBM).
title_short Saponin 1 induces apoptosis and suppresses NF-κB-mediated survival signaling in glioblastoma multiforme (GBM).
title_full Saponin 1 induces apoptosis and suppresses NF-κB-mediated survival signaling in glioblastoma multiforme (GBM).
title_fullStr Saponin 1 induces apoptosis and suppresses NF-κB-mediated survival signaling in glioblastoma multiforme (GBM).
title_full_unstemmed Saponin 1 induces apoptosis and suppresses NF-κB-mediated survival signaling in glioblastoma multiforme (GBM).
title_sort saponin 1 induces apoptosis and suppresses nf-κb-mediated survival signaling in glioblastoma multiforme (gbm).
publisher Public Library of Science (PLoS)
publishDate 2013
url https://doaj.org/article/360bfc0babcd48bf8c9603898a4968b7
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