6-Dehydrogingerdione sensitizes human hepatoblastoma hep G2 cells to trail-induced apoptosis via reactive oxygen species-mediated increase of dr5

Chung Yi Chen, Cheng Jeng Tai, Jiin Tsuey Cheng, Juan Juan Zheng, Ying Zong Chen, Tsan Zon Liu, Shuenn Jiun Yiin, Chi Liang Chern

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

The anticancer effects of 6-dehydrogingerdione (6-DG), a compound isolated from the rhizomes of Zingiber officinale, and its mechanisms of sensitization to TRAIL-induced apoptosis were studied using human hepatoblastoma Hep G2 cells. This study demonstrates for the first time that 6-DG-induced apoptosis might be executed via mitochondrial-and Fas receptor-mediated pathways. Further studies also demonstrated that 6-DG could sensitize Hep G2 cells to TRAIL-induced apoptosis. 6-DG also up-regulated Ser-15 phosphorylation and evoked p53 nuclear translocation. Abrogation of p53 expression by p53 small interfering RNA significantly attenuated 6-DG-induced DR5 expression, thus rendering these cells resistant to TRAIL-induced apoptosis. DR5 expression after 6-DG treatment was accompanied by provoking intracellular reactive oxygen species (ROS) generation. Pretreatment with N-acetyl-l-cysteine (NAC) attenuated 6-DG-induced DR5 expression and inhibited TRAIL-induced apoptosis. In contrast to Hep G2 cells, DR5 up-regulation and sensitization to TRAIL-induced apoptosis instigated by 6-DG were not observed in normal MDCK cells. Taken together, these data suggested that in addition to the mitochondrial-and Fas receptor-mediated apoptotic pathways involved, ROS-dependent and p53-regulated DR5 expression was also demonstrated to play a pivotal role in the synergistic enhancement of TRAIL-induced apoptosis instigated by 6-DG in Hep G2 cells.

Original languageEnglish
Pages (from-to)5604-5611
Number of pages8
JournalJournal of Agricultural and Food Chemistry
Volume58
Issue number9
DOIs
Publication statusPublished - May 12 2010

Keywords

  • 6-dehydrogingerdione
  • Apoptosis
  • DR5
  • Reactive oxygen species

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Chemistry(all)

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