Abstract
Tubeimoside-1 is a triterpenoid saponin extracted from the traditional Chinese herb Bolbostemma paniculatum (Maxim.) Franquet (Cucurbitaceae). We investigated the cytotoxic effect and apoptosis mechanism of tubeimoside-1. Tubeimoside-1 was cytotoxic in seven human cancer cell lines, with HepG2 the most sensitive. Tubeimoside-1 induced apoptosis of HepG2 cells dose and time dependently. Both the extrinsic and intrinsic pathways were triggered by tubeimoside-1. Caspase-3, -8 and -9 were activated and the expression of Fas, Fas ligand, Bcl-2, Bak and Bax was regulated. Moreover, tubeimoside-1 induced accumulation of reactive oxygen species and arrested cell cycle at the G(2)/M phase, thus contributing to apoptosis, through signaling regulation by tumor necrosis factor α, nuclear factor κB (NF-κB), Jun N-terminal kinase (JNK) and p53. We provide further insight into the tubeimoside-1 cytotoxic effect for antitumor chemotherapeutic treatment.
Copyright © 2011 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Apoptosis / drug effects*
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Caspase 3 / genetics
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Caspase 3 / metabolism
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Caspase 8 / genetics
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Caspase 8 / metabolism
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Caspase 9 / genetics
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Caspase 9 / metabolism
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Cucurbitaceae / chemistry
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Drugs, Chinese Herbal / pharmacology
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Fas Ligand Protein / genetics
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Fas Ligand Protein / metabolism
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G2 Phase Cell Cycle Checkpoints / drug effects*
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Gene Expression Regulation
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Hep G2 Cells
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Humans
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JNK Mitogen-Activated Protein Kinases / genetics
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JNK Mitogen-Activated Protein Kinases / metabolism*
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NF-kappa B / genetics
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NF-kappa B / metabolism*
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Oxidative Stress / drug effects*
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Reactive Oxygen Species / metabolism
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Saponins / pharmacology*
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Signal Transduction
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Triterpenes / pharmacology*
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Tumor Necrosis Factor-alpha / genetics
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Tumor Necrosis Factor-alpha / metabolism
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Tumor Suppressor Protein p53 / genetics
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Tumor Suppressor Protein p53 / metabolism*
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bcl-2-Associated X Protein / genetics
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bcl-2-Associated X Protein / metabolism
Substances
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Drugs, Chinese Herbal
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Fas Ligand Protein
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NF-kappa B
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Reactive Oxygen Species
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Saponins
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TP53 protein, human
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Triterpenes
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Tumor Necrosis Factor-alpha
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Tumor Suppressor Protein p53
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bcl-2-Associated X Protein
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tubeimoside I
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JNK Mitogen-Activated Protein Kinases
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CASP3 protein, human
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CASP8 protein, human
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CASP9 protein, human
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Caspase 3
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Caspase 8
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Caspase 9