Fisetin Induces Apoptosis Through p53-Mediated Up-Regulation of DR5 Expression in Human Renal Carcinoma Caki Cells.

Kyoung-jin Min,Taeg Kwon,Ju-Ock Nam

doi:10.3390/molecules22081285

Kyoung-jin Min, Taeg Kwon + Show 1 more

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https://doi.org/10.3390/molecules22081285

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Abstract

Fisetin is a natural compound found in fruits and vegetables such as strawberries, apples, cucumbers, and onions. Since fisetin can elicit anti-cancer effects, including anti-proliferation and anti-migration, we investigated whether fisetin induced apoptosis in human renal carcinoma (Caki) cells. Fisetin markedly induced sub-G1 population and cleavage of poly (ADP-ribose) polymerase (PARP), which is a marker of apoptosis, and increased caspase activation. We found that pan-caspase inhibitor (z-VAD-fmk) inhibited fisetin-induced apoptosis. In addition, fisetin induced death receptor 5 (DR5) expression at the transcriptional level, and down-regulation of DR5 by siRNA blocked fisetin-induced apoptosis. Furthermore, fisetin induced p53 protein expression through up-regulation of protein stability, whereas down-regulation of p53 by siRNA markedly inhibited fisetin-induced DR5 expression. In contrast, fisetin induced up-regulation of CHOP expression and reactive oxygen species production, which had no effect on fisetin-induced apoptosis. Taken together, our study demonstrates that fisetin induced apoptosis through p53 mediated up-regulation of DR5 expression at the transcriptional level.

Highlights

IntroductionFisetin has anti-cancer effects in several types of cancer cells [3,6,7]
death receptor 5 (DR5) protein to the plasma membrane is important for death receptors (DRs)-mediated apoptosis, translocation of the DR5 protein to the plasma membrane is important for DR-mediated apoptosis, we we examined examined whether whether fisetin fisetin increases increases DR5
Our results together, our results demonstrate that fisetin induces apoptosis through p53-mediated demonstrate that fisetin induces apoptosis through p53-mediated up-regulation of DR5 expression in up-regulation of DR5 expression in human renal carcinoma Caki cells

Summary

Introduction

Fisetin has anti-cancer effects in several types of cancer cells [3,6,7]. Fisetin induces apoptosis via inhibition of the MAPK signaling pathway in human non-small cell lung cancer [7] and reactive oxygen species (ROS) production in human oral cancer cells [8]. Fisetin has a sensitizing effect in anti-cancer therapy. Combined treatment with fisetin and cabazitaxol has been shown to induce apoptosis [9]. Treatment with fisetin enhanced tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis in cancer cells [10]. The molecular mechanism of this anti-cancer effect by fisetin is not well understood

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