title: Saponin 1 induces apoptosis and suppresses NF-κB-mediated survival signaling in glioblastoma multiforme (GBM).
abstract: 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.
authors.affiliation: Department of Neurosurgery, Xijing Institute of Clinical Neuroscience, Fourth Military Medical University, Xi'an, China ; Faculty of Biomedical Engineering, Fourth Military Medical University, Xi'an, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Li
authors.forename: Haifeng
authors.initials: H
authors.lastname: Tang
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
authors.forename: Chi
authors.initials: C
authors.lastname: Tang
authors.forename: Bo
authors.initials: B
authors.lastname: Li
authors.forename: Yuangang
authors.initials: Y
authors.lastname: Wang
authors.forename: Zhenhui
authors.initials: Z
authors.lastname: Gao
authors.forename: Peng
authors.initials: P
authors.lastname: Luo
authors.forename: Anan
authors.initials: A
authors.lastname: Yin
authors.forename: Xiaoyang
authors.initials: X
authors.lastname: Wang
authors.forename: Guang
authors.initials: G
authors.lastname: Cheng
authors.forename: Zhou
authors.initials: Z
authors.lastname: Fei
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001932:Brain Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005909:Glioblastoma / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018922:HL-60 Cells; D056945:Hep G2 Cells; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D010936:Plant Extracts / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology; D021381:Protein Transport; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D012503:Saponins / Q000008:administration & dosage / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D047368:Tumor Burden / Q000187:drug effects; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000235:genetics / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D016328:NF-kappa B; D010936:Plant Extracts; D019253:Proto-Oncogene Proteins c-bcl-2; D012503:Saponins; D051636:X-Linked Inhibitor of Apoptosis Protein; D051028:bcl-2-Associated X Protein; D053148:Caspase 3; D053453:Caspase 9