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), 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.
Highlights
Garcinol is a polyisoprenylated benzophenone which may be isolated from the dried rind of the fruit Garcinia indica
To investigate whether garcinol enhances TRAIL sensitization, we employed renal carcinoma Caki cells that are resistant to TRAIL
Levels of apoptosis were assessed by flow cytometry an western blot showing the PARP, c-FLIP and actin. * p < 0.01 compared to the control. # p < 0.01 compared to the garcinol plus TRAIL. ** p < 0.01 compared to the garcinol plus
Summary
Garcinol is a polyisoprenylated benzophenone which may be isolated from the dried rind of the fruit Garcinia indica It exhibits multiple biological effects, such as anti-inflammatory, anti-microbial an anti-oxidative activities [1,2,3]. New approaches to overcome TRAIL resistance that combined treatment with pharmacological agents that modify the function of tumor-dysregulated apoptotic genes have been investigated [15,16,17]. In this present study, we investigated the molecular mechanisms involved in the sensitizing effect of garcinol on TRAIL-induced apoptosis in cancer cells
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