Licochalcone-A sensitizes human esophageal carcinoma cells to TRAIL-mediated apoptosis by proteasomal degradation of XIAP

Hepatogastroenterology. 2014 Jul-Aug;61(133):1229-34.

Abstract

Background/aims: Esophageal carcinoma is one of the most aggressive human cancers, and novel treatment modality is required. Although expressing adequate levels of functional tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptors DR4/DR5, significant proportion of esophageal cancer cells exhibit resistance to the cytotoxic effect of this ligand. Licochalcone-A (LA), a flavonoid present in a variety of edible plants, exhibits a wide spectrum of pharmacologic properties such as anticancer, antioxidant, and anti-inflammatory activities.

Methodology: Eca109 and TE1 cells were cultured and transfected, then their viability was detected using MTT assay. Immunoprecipitation and immunoblotting analysis and RT-PCR analysis were also performed.

Results: In this study, we found that LA synergistically caused the TRAIL-induced apoptosis in Eca109 and TE1 cells. Such potentiation was achieved through inhibiting Akt activation and promoting proteasomal degradation of X-linked Inhibitor of Apoptosis Protein (XIAP) which mediated the survival signals and allow the cells to escape from apoptosis in various human cancers.

Conclusions: The combination of TRAIL and LA might be a novel therapeutic strategy for esophageal carcinoma patients who fail to respond to standard chemotherapy.

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology*
  • Apoptosis / drug effects*
  • Carcinoma / enzymology*
  • Carcinoma / pathology
  • Cell Line, Tumor
  • Chalcones / pharmacology
  • Dose-Response Relationship, Drug
  • Drug Synergism
  • Esophageal Neoplasms / enzymology*
  • Esophageal Neoplasms / genetics
  • Esophageal Neoplasms / pathology
  • HEK293 Cells
  • Humans
  • Proteasome Endopeptidase Complex / metabolism*
  • Proteolysis
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism
  • TNF-Related Apoptosis-Inducing Ligand / pharmacology
  • Time Factors
  • Transfection
  • X-Linked Inhibitor of Apoptosis Protein / metabolism*

Substances

  • Antineoplastic Agents, Phytogenic
  • Chalcones
  • TNF-Related Apoptosis-Inducing Ligand
  • TNFSF10 protein, human
  • X-Linked Inhibitor of Apoptosis Protein
  • XIAP protein, human
  • Proto-Oncogene Proteins c-akt
  • Proteasome Endopeptidase Complex
  • licochalcone A