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NF-κB, JNK and p53 pathways are involved in tubeimoside-1-induced apoptosis in HepG2 cells with oxidative stress and G₂/M cell cycle arrest.

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.
AuthorsYan Yin, Wei Chen, Changyan Tang, Hanjing Ding, Jongchol Jang, Meizhi Weng, Yongjun Cai, Guolin Zou
JournalFood and chemical toxicology : an international journal published for the British Industrial Biological Research Association (Food Chem Toxicol) Vol. 49 Issue 12 Pg. 3046-54 (Dec 2011) ISSN: 1873-6351 [Electronic] England
PMID22005259 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2011 Elsevier Ltd. All rights reserved.
Chemical References
  • Drugs, Chinese Herbal
  • Fas Ligand Protein
  • NF-kappa B
  • Reactive Oxygen Species
  • Saponins
  • TP53 protein, human
  • Triterpenes
  • Tumor Necrosis Factor-alpha
  • Tumor Suppressor Protein p53
  • bcl-2-Associated X Protein
  • tubeimoside I
  • JNK Mitogen-Activated Protein Kinases
  • CASP3 protein, human
  • CASP8 protein, human
  • CASP9 protein, human
  • Caspase 3
  • Caspase 8
  • Caspase 9
Topics
  • Apoptosis (drug effects)
  • Caspase 3 (genetics, metabolism)
  • Caspase 8 (genetics, metabolism)
  • Caspase 9 (genetics, metabolism)
  • Cucurbitaceae (chemistry)
  • Drugs, Chinese Herbal (pharmacology)
  • Fas Ligand Protein (genetics, metabolism)
  • G2 Phase Cell Cycle Checkpoints (drug effects)
  • Gene Expression Regulation
  • Hep G2 Cells
  • Humans
  • JNK Mitogen-Activated Protein Kinases (genetics, metabolism)
  • NF-kappa B (genetics, metabolism)
  • Oxidative Stress (drug effects)
  • Reactive Oxygen Species (metabolism)
  • Saponins (pharmacology)
  • Signal Transduction
  • Triterpenes (pharmacology)
  • Tumor Necrosis Factor-alpha (genetics, metabolism)
  • Tumor Suppressor Protein p53 (genetics, metabolism)
  • bcl-2-Associated X Protein (genetics, metabolism)

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