Gypenosides induced G0/G1 arrest via CHk2 and apoptosis through endoplasmic reticulum stress and mitochondria-dependent pathways in human tongue cancer SCC-4 cells

Jung Chou Chen, Kung Wen Lu, Ming Li Tsai, Shu Chun Hsu, Chao Lin Kuo, Jai Sing Yang, Te Chun Hsia, Chun Shu Yu, Su Tze Chou, Ming Ching Kao, Jing Gung Chung, W. Gibson Wood

Research output: Contribution to journalArticlepeer-review

82 Scopus citations

Abstract

Gypenosides (Gyp), a component of Gynostemma pentaphyllum Makino, was selected for examining the effects on the cell viability, cell cycle and induction of apoptosis in human tongue cancer SCC-4 cells. Gyp induced cytotoxicity (decreased the percentage of viable cells) in SCC-4 cells appeared to be associated with induction of cell cycle arrest (G0/G1 arrest), apoptotic cell death based on Gyp induced morphological changes and DNA fragmentation and increased the sub-G1 group in examined SCC-4 cells. The production of reactive oxygen species and Ca2+ and the depolarization of mitochondrial membrane potential were observed, dose- and time-dependently, after treatment of SCC-4 cells with various concentrations of Gyp. Gyp inhibited the levels of the anti-apoptotic proteins Bcl-2 and Bcl-xl, but promoted the levels of the pro-apoptotic protein Bax. Western blotting showed the releases of cytochrome c and Endo G and both were also confirmed by confocal laser microscopic systems. The GADD153 moved to nuclei (nuclear translocation). In conclusion, Gyp induced ER stress and production of reactive oxygen species and Ca2+, change the ratio of Bcl-2 and Bax, followed by the dysfunction of mitochondria, caused cytochrome c release, activation of caspase-3 before leading to apoptosis. These results provide information towards an understanding of the mechanisms by which Gyp induces cell cycle arrest and apoptosis in human tongue cancer cells. Crown

Original languageEnglish (US)
Pages (from-to)273-283
Number of pages11
JournalOral Oncology
Volume45
Issue number3
DOIs
StatePublished - Mar 2009

Bibliographical note

Funding Information:
This work was supported by Grants CMU95-327 and CMU95-330 from the China Medical University of Taiwan.

Copyright:
Copyright 2010 Elsevier B.V., All rights reserved.

Keywords

  • Apoptosis
  • Cell cycle arrest
  • Cytochrome c
  • Gypenosides
  • Oral
  • Oral cancer
  • SCC-4 cells

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