# Chrysoeriol Chemosensitized Renal Cell Carcinoma (RCC) Cell Lines to Trigger TRAIL Induced Apoptosis In Vitro by Up‐Regulating Pro‐Apoptotic and Down‐Regulating Anti‐Apoptotic Genetic Factors

## TL;DR

Chrysoeriol makes kidney cancer cells more responsive to TRAIL treatment, helping to trigger cell death in lab experiments.

## Contribution

This is the first study to show chrysoeriol's chemo-sensitizing effect on TRAIL-resistant renal carcinoma cells.

## Key findings

- Chrysoeriol synergized with TRAIL to induce apoptosis in resistant renal carcinoma cells.
- The treatment increased pro-apoptotic gene expression and decreased anti-apoptotic gene activity.
- It also triggered mitochondrial dysfunction and proteasome inhibition in cancer cells.

## Abstract

Renal carcinoma is a lethal cancer, researched by several studies to get insights into the molecular causes of disease, in order to come up with advanced therapeutic treatments. Tumor necrosis factor‐related apoptosis‐inducing ligand (TRAIL), is an anticancer cytokine posing therapeutic effects to treat cancer. However, certain cancer types including renal cell carcinoma developed resistance towards TRAIL, hence limiting its usefulness in cancer treatment. Recently, synergistic approach has been emerged in clinical settings to sensitize cancer cells towards TRAIL treatment by combining with natural antioxidants and anti‐inflammatory compounds for providing chemo‐sensitizing effects. Hence, this study has used chemo‐sensitizing effect of chrysoeriol for the very first time to sensitize renal carcinoma cell lines for treatment with TRAIL by synergistic treatment approach, in vitro. The effects of 20 μM chrysoeriol, 50 ng/mL TRIAL and their synergistic combination were investigated deeply by adopting different experimental strategies in vitro. Synergistic combination of 20 μM chrysoeriol/50 ng/mL TRIAL provided apoptosis of TRAIL resistant cell lines which was confirmed by increasing the expressions of caspases including caspase‐3 and caspase‐8 and caspase‐9, increasing the expression of interleukins 10, while decreasing the expression of interleukins 6, triggering cellular apoptosis, inhibiting proteasome activity, lossing mitochondrial membrane potential and triggering cytchrome C release. Meanwhile, rise in death receptor 4 expression as well as up‐regulation of pro‐apoptotic and down‐regulation of anti‐apoptotic genes further provided evidence for chemo‐sensitizing effect of chrysoeriol on TRAIL resistant renal carcinoma cells to trigger apoptosis. Hence, chrysoeriol could be employed in the anticancer drug development for therapeutic treatment of renal cancer.

Recently, a synergistic approach has emerged in clinical settings to sensitize cancer cells towards TRAIL treatment by combining it with some natural antioxidants and anti‐inflammatory compounds for providing chemo‐sensitizing effects. Hence, this study has used the chemo‐sensitizing effect of chrysoeriol for the very first time to sensitize renal carcinoma cell lines for treatment with TRAIL by a synergistic treatment approach, in vitro.