Tubeimoside-1 induces G2/M phase arrest and apoptosis in SKOV-3 cells through increase of intracellular Ca²⁺ and caspase-dependent signaling pathways

Int J Oncol. 2012 Feb;40(2):535-43. doi: 10.3892/ijo.2011.1218. Epub 2011 Oct 3.

Abstract

Tubeimoside-1 (TBMS1) extracted from Bolbostemma paniculatum (Maxim), is a traditional Chinese herb with anticancer potential. It induces apoptosis in a number of human carcinoma cell lines, but the mechanism has remained unclear. In the present study, we investigated the pro-apoptotic activity of TBMS1 against SKOV-3 cell lines and the underlying mechanisms. Treatment with TBMS1 resulted in dose- and time-dependent inhibition of proliferation, led to arrest in phase G2/M of the cell cycle and increased the levels of intracellular Ca²⁺. Furthermore, TBMS1 up-regulated the levels of the glucose-regulated protein 78/immunoglobuin heavy chain binding protein (GRP78/Bip), C/EBP homologous protein (CHOP), Bax, and cleaved caspase-3 and down-regulated the levels of Bcl-2. It was shown to be linked to activation of the extracellular signal-regulated kinase (ERK) 1 and 2 signal transduction pathway. A decrease in Bcl-2/Bax ratio with increased expression of caspase-3, and intracellular Ca²⁺ provide compelling evidence that TBMS1-induced apoptosis is mediated by the mitochondrial pathway. The results of the present study suggest that TBMS1 has immense potential in cancer prevention and therapy based on its antiproliferative and apoptosis inducing effects.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • Calcium Signaling*
  • Caspase 3 / metabolism*
  • Cell Line, Tumor
  • Cell Proliferation
  • Cell Survival / drug effects
  • Drugs, Chinese Herbal
  • Endoplasmic Reticulum / metabolism
  • Enzyme Activation
  • G2 Phase Cell Cycle Checkpoints / drug effects*
  • Gene Expression
  • Heat-Shock Proteins / metabolism
  • Humans
  • Mitogen-Activated Protein Kinases / metabolism
  • Oligopeptides / metabolism
  • Phosphorylation
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Saponins / pharmacology*
  • Transcription Factor CHOP / metabolism
  • Triterpenes / pharmacology*
  • bcl-2-Associated X Protein / genetics
  • bcl-2-Associated X Protein / metabolism

Substances

  • BAX protein, human
  • Bax-inhibiting peptide, BIP
  • DDIT3 protein, human
  • Drugs, Chinese Herbal
  • Heat-Shock Proteins
  • Oligopeptides
  • Proto-Oncogene Proteins c-bcl-2
  • Saponins
  • Triterpenes
  • bcl-2-Associated X Protein
  • tubeimoside I
  • Transcription Factor CHOP
  • Mitogen-Activated Protein Kinases
  • CASP3 protein, human
  • Caspase 3
  • molecular chaperone GRP78