Garcinol enhances TRAIL-induced apoptotic cell death through up-regulation of DR5 and down-regulation of c-FLIP expression

Seok Kim, Seung Un Seo, Kyoung Jin Min, Seon Min Woo, Ju Ock Nam, Peter Kubatka, Shin Kim, Jong Wook Park, Taeg Kyu Kwon

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

Garcinol is a polyisoprenylated benzophenone derived from the Garcinia indica fruit that possess potential therapeutic effects such as inhibition of inflammation and tumor expansion. Here, we investigated whether garcinol induces TRAIL sensitization in renal carcinoma cells. Single treatment with garcinol or TRAIL did not effect on apoptosis. However, combined treatment with garcinol plus TRAIL significantly induced apoptosis in renal carcinoma (Caki, ACHN and A498), lung carcinoma (A549) an hepatoma (SK-Hep1) cells. In contrast, garcinol plus TRAIL did not alter cell viability in normal cells. Garcinol plus TRAIL induced up-regulation of DR5 and down-regulation of c-FLIP expression at post-translational levels. Furthermore, knock-down of DR5 by siRNA and ectopic expression of c-FLIP blocked apoptotic cell death induced by garcinol plus TRAIL. Overall, our study provides evidence that garcinol can be exploited as a potential TRAIL sensitizer.

Original languageEnglish
Article number1614
JournalMolecules
Volume23
Issue number7
DOIs
StatePublished - 2018

Keywords

  • Apoptosis
  • C-FLIP
  • DR5
  • Garcinol
  • TRAIL

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