Angelicin potentiates TRAIL-induced apoptosis in renal carcinoma Caki cells through activation of caspase 3 and down-regulation of c-FLIP expression

Drug Dev Res. 2018 Feb;79(1):3-10. doi: 10.1002/ddr.21414. Epub 2017 Oct 16.

Abstract

Preclinical Research & Development Angelicin is a furocoumarin derived from Psoralea corylifolia L. fruit that has anti-inflammatory and anti-tumor activity. In the present study, the effect of angelicin in enhancing tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptotic cell death was studied in Caki (renal carcinoma) cells. Angelicin alone and TRAIL alone had no effect on apoptosis, but in combination these compounds markedly induced apoptosis in the cancer cell lines while not inducing apoptosis in normal cells. The combination treatment induced accumulation of the sub-G1 population, DNA fragmentation, and activated caspase 3 activity in Caki cells, induced down-regulation of c-FLIP expression post-translationally, and over-expression of c-FLIP markedly blocked apoptosis induced by combined treatment with angelicin plus TRAIL. This study provides evidence that angelicin might be a TRAIL sensitizer.

Keywords: TRAIL; angelicin; apoptosis; c-FLIP; caspase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • CASP8 and FADD-Like Apoptosis Regulating Protein / genetics*
  • CASP8 and FADD-Like Apoptosis Regulating Protein / metabolism*
  • Carcinoma, Renal Cell / drug therapy
  • Carcinoma, Renal Cell / metabolism
  • Caspase 3 / metabolism*
  • Cell Line, Tumor
  • Cells, Cultured
  • DNA Fragmentation
  • Down-Regulation
  • Drug Synergism
  • Fibroblasts
  • Furocoumarins / pharmacology*
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Kidney Neoplasms / drug therapy
  • Kidney Neoplasms / metabolism
  • TNF-Related Apoptosis-Inducing Ligand / pharmacology*

Substances

  • CASP8 and FADD-Like Apoptosis Regulating Protein
  • CFLAR protein, human
  • Furocoumarins
  • TNF-Related Apoptosis-Inducing Ligand
  • angelicin
  • CASP3 protein, human
  • Caspase 3