Dandelion Root Extract Enhances the Toxicity of Sunitinib to Renal Cell Carcinoma Cells by Inducing Mitochondrial Dysfunction and Triggering Apoptosis

Abstract

Background: At present, sunitinib (ST) is the most frequently used targeted therapy drug for renal cell carcinoma (RCC). The objective of this study was to investigate whether dandelion root extract (DRE) could improve the curative effect of ST on RCC through in vitro experiments. Methods: First, 786-O human RCC cells were divided into Control, DRE, ST and DRE+ST groups. Next, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) and colony formation assays were applied to test the proliferation and viability of 786-O cells, respectively. Cell apoptosis, reactive oxygen species (ROS) levels and changes in mitochondrial membrane potential were detected by flow cytometry. Western blot was used to evaluate protein expression levels of B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), Caspase-3, cleaved-Caspase-3, Caspase-9, apoptosis-inducing factor (AIF), cytochrome c (Cyt-c), cleaved-Caspase-9 and cleaved-poly ADP-ribose polymerase (PARP) in mitochondria. Besides, mitochondrial DNA (mtDNA) content and expression levels of peroxisome proliferator-activated receptor-gamma co-activator-1alpha (PGC-1α), mitochondrial transcription factor A (TFAM), dynamin-related protein 1 (DRP1), mitofusin 1/2 (MFN1/2) were measured by real-time fluorescence quantitative polymerase chain reaction (qRT-PCR). Results: Compared with DRE alone or ST alone, DRE combined with ST significantly increased the toxicity of 786-O cells (p < 0.01), increased ROS accumulation (p < 0.01), promoted apoptosis (p < 0.01), up-regulated the expression level of mitochondrial apoptosis-related proteins (p < 0.01), decreased mitochondrial membrane potential (p < 0.01), and induced mitochondrial dysfunction in 786-O cells (p < 0.01). Conclusions: DRE may increase the toxicity of ST to RCC cells via inducing mitochondrial dysfunction and triggering apoptosis. Therefore, DRE combined with ST may be a potential treatment option for RCC.