Flavokawain B, a novel chalcone from Alpinia pricei Hayata with potent apoptotic activity: Involvement of ROS and GADD153 upstream of mitochondria-dependent apoptosis in HCT116 cells

Free Radic Biol Med. 2010 Jul 15;49(2):214-26. doi: 10.1016/j.freeradbiomed.2010.04.005. Epub 2010 Apr 14.


Flavonoids synthesized from chalcone precursors in plants have been shown to possess cytotoxic activities with therapeutic potential. We have isolated the novel chalcone flavokawain B from Alpinia pricei Hayata, a plant native to Taiwan that is used in food and traditional Chinese medicine. Here, we report for the first time that flavokawain B significantly inhibits the growth of colon cancer cells and provide novel insight into the molecular mechanisms that underlie its apoptotic activity. Flavokawain B exerts its apoptotic action through ROS generation and GADD153 up-regulation, which lead to mitochondria-dependent apoptosis characterized by release of cytochrome c and translocation of Bak. The up-regulation of GADD153 in flavokawain B-treated HCT116 cells is associated with mitochondrial dysfunction and altered expression of Bcl-2 family members. Moreover, pretreatment with the ROS scavenger N-acetylcysteine abolishes flavokawain B-induced ROS generation, GADD153 up-regulation, and apoptosis. Similarly, RNAi-mediated gene silencing reduced flavokawain B-enhanced expression of GADD153 and apoptotic Bim, leading to diminished apoptosis. Interestingly, flavokawain B provokes G2/M accumulation as well as autophagy, in addition to apoptosis, suggesting that multiple pathways are activated in flavokawain B-mediated anticancer activity. Taken together, our data provide evidence for a molecular mechanism to explain the apoptotic activity of Alpinia plants, showing that flavokawain B acts through ROS generation and GADD153 up-regulation to regulate the expression of Bcl-2 family members, thereby inducing mitochondrial dysfunction and apoptosis in HCT116 cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alpinia
  • Apoptosis* / drug effects
  • Apoptosis* / genetics
  • Cytochromes c / metabolism
  • Flavonoids / pharmacology*
  • Gene Expression Regulation
  • HCT116 Cells
  • Humans
  • Medicine, Chinese Traditional
  • Mitochondria / drug effects
  • Mitochondria / metabolism*
  • Proto-Oncogene Proteins c-bcl-2 / biosynthesis*
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • RNA, Small Interfering / genetics
  • Reactive Oxygen Species / metabolism
  • Signal Transduction / drug effects
  • Signal Transduction / genetics
  • Transcription Factor CHOP / genetics
  • Transcription Factor CHOP / metabolism*


  • Flavonoids
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Small Interfering
  • Reactive Oxygen Species
  • flavokawain B
  • Transcription Factor CHOP
  • Cytochromes c