Arctigenin suppresses unfolded protein response and sensitizes glucose deprivation-mediated cytotoxicity of cancer cells

Planta Med. 2011 Jan;77(2):141-5. doi: 10.1055/s-0030-1250179. Epub 2010 Aug 17.


The involvement of unfolded protein response (UPR) activation in tumor survival and resistance to chemotherapies suggests a new anticancer strategy targeting UPR pathway. Arctigenin, a natural product, has been recently identified for its antitumor activity with selective toxicity against cancer cells under glucose starvation with unknown mechanism. Here we found that arctigenin specifically blocks the transcriptional induction of two potential anticancer targets, namely glucose-regulated protein-78 (GRP78) and its analog GRP94, under glucose deprivation, but not by tunicamycin. The activation of other UPR pathways, e.g., XBP-1 and ATF4, by glucose deprivation was also suppressed by arctigenin. A further transgene experiment showed that ectopic expression of GRP78 at least partially rescued arctigenin/glucose starvation-mediated cell growth inhibition, suggesting the causal role of UPR suppression in arctigenin-mediated cytotoxicity under glucose starvation. These observations bring a new insight into the mechanism of action of arctigenin and may lead to the design of new anticancer therapeutics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activating Transcription Factor 4 / drug effects
  • Activating Transcription Factor 4 / genetics
  • Animals
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • DNA-Binding Proteins / drug effects
  • DNA-Binding Proteins / genetics
  • Furans / pharmacology*
  • Gene Expression Regulation, Neoplastic / drug effects
  • Glucose / metabolism*
  • Glucose / pharmacology
  • HSP70 Heat-Shock Proteins / drug effects
  • HSP70 Heat-Shock Proteins / genetics
  • Humans
  • Lignans / pharmacology*
  • Membrane Proteins / drug effects
  • Membrane Proteins / genetics
  • Regulatory Factor X Transcription Factors
  • Time Factors
  • Transcription Factors / drug effects
  • Transcription Factors / genetics
  • Transcriptional Activation / drug effects*
  • Unfolded Protein Response / drug effects*
  • Unfolded Protein Response / genetics
  • X-Box Binding Protein 1


  • Antineoplastic Agents, Phytogenic
  • DNA-Binding Proteins
  • Furans
  • HSP70 Heat-Shock Proteins
  • Lignans
  • Membrane Proteins
  • Regulatory Factor X Transcription Factors
  • Transcription Factors
  • X-Box Binding Protein 1
  • XBP1 protein, human
  • glucose-regulated proteins
  • Activating Transcription Factor 4
  • Glucose
  • arctigenin