Quercetrin from Toona sinensis leaves induces cell cycle arrest and apoptosis via enhancement of oxidative stress in human colorectal cancer SW620 cells

Finding effective strategies against colorectal cancer (CRC) is still an emergent health problem. In the present study, we investigated the anticancer activity of quercetrin from Toona sinensis leaves (QTL) and explored the underlying mechanism in human CRC cell line SW620. The cells were treated with various concentrations of QTL and the cytotoxic effects of QTL were determined using the MTT assay. Apoptosis and cell cycle status were detected by flow cytometry. Reactive oxygen species (ROS) levels and mitochondrial membrane potential (∆Ψm) were assessed using DCF-DA and JC-1 fluorescence spectrophotometry, respectively. Western blot analysis was used to quantify the expression of apoptosis-related proteins. RT-PCR was applied to determine the mRNA levels of glutathione peroxidase (GPx) and catalase (CAT). QTL exhibited growth inhibitory effects and caused cell cycle arrest in the G2/M phase, which was accompanied by increased expression of p53 and p21 proteins. QTL promoted apoptosis which was consistent with the upregulated expression of Bax, cytochrome c, caspase-9, Apaf-1 and caspase-3. In addition, QTL induced the loss of mitochondrial membrane potential and triggered ROS generation, as revealed by the downregulated mRNA expression and enzymatic activity of GPx and CAT. Furthermore, both N-acetyl cysteine (NAC) and GSH attenuated the QTL-induced growth inhibition observed in SW620 cells along with the increase of ROS levels. These findings revealed that QTL inhibited the growth of CRC cells and facilitated apoptosis by enhancing oxidative stress. QTL may therefore have potential for use in CRC chemotherapy.