Gypenosides suppress growth of human oral cancer SAS cells in vitro and in a murine xenograft model: The role of apoptosis mediated by caspase-dependent and caspase-independent pathways

Kung Wen Lu, Jung Chou Chen, Tung Yuan Lai, Jai Sing Yang, Shu Wen Weng, Yi Shih Ma, Hui Yi Lin, Rick Sai Chuan Wu, King Chuen Wu, W. Gibson Wood, Jing Gung Chung

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

Purpose. Gypenosides (Gyp) are the major components of Gynostemma pentaphyllum Makino. The authors investigated the effects of Gyp on cell morphology, viability, cell cycle distribution, and induction of apoptosis in human oral cancer SAS cells and the determination of murine SAS xenograft model in vivo. Experimental design. Flow cytometry was used to quantify the percentage of viable cells; cell cycle distribution; sub-G1 phase (apoptosis); caspase-3, -8, and -9 activity; reactive oxygen species (ROS) production, intracellular Ca2+ determination; and the level of mitochondrial membrane potential (δψm). Western blotting was used to examine levels of apoptosis-associated proteins, and confocal laser microscopy was used to examine the translocation of proteins in cells. Results. Gyp induced morphological changes, decreased the percentage of viable cells, caused G0/G1 phase arrest, and triggered apoptotic cell death in SAS cells. Cell cycle arrest induced by Gyp was associated with apoptosis. The production of ROS, increased intracellular Ca2+ levels, and the depolarization of δψm were observed. Gyp increased levels of the proapoptotic protein Bax but inhibited the levels of the antiapoptotic proteins Bcl-2 and Bcl-xl. Gyp also stimulated the release of cytochrome c and Endo G. Translocation of GADD153 to the nucleus was stimulated by Gyp. Gyp in vivo attenuated the size and volume of solid tumors in a murine xenograft model of oral cancer. Conclusions. Gyp-induced cell death occurs through caspase-dependent and caspase-independent apoptotic signaling pathways, and the compound reduced tumor size in a xenograft nu/nu mouse model of oral cancer.

Original languageEnglish (US)
Pages (from-to)129-140
Number of pages12
JournalIntegrative Cancer Therapies
Volume11
Issue number2
DOIs
StatePublished - Jun 1 2012

Keywords

  • caspase cascade
  • caspase independent
  • gypenosides
  • human oral cancer SAS cells
  • murine xenograft model
  • traditional Chinese medicine

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