Garcinol Enhances TRAIL-Induced Apoptotic Cell Death through Up-Regulation of DR5 and Down-Regulation of c-FLIP Expression.

Molecules 2018 Jul 2;23(7). Epub 2018 Jul 2.

Department of Immunology and School of Medicine, Keimyung University, 2800 Dalgubeoldaero, Dalseo-Gu, Daegu 42601, Korea.

Garcinol is a polyisoprenylated benzophenone derived from the 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), and 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.

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Source
http://dx.doi.org/10.3390/molecules23071614DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6099973PMC
July 2018

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