Quercetin preferentially induces apoptosis in KRAS-mutant colorectal cancer cells via JNK signaling pathways

摘要

Colorectal cancer (CRC) is the third most common type of cancer, and its incidence and mortality are markedly increasing worldwide. Oncogenic mutations of KRAS occur in up to 40% of CRC cases and pose a great challenge in the treatment of the disease. Quercetin is a dietary flavonoid that exerts anti-oxidant, anti-inflammatory, and anti-cancer properties. The current study investigated the anti-proliferative effect of quercetin on CRC cells harboring mutant or wild-type KRAS. The effect of quercetin on cell viability was investigated by MTT and colony formation assays, and apoptosis was detected using flow cytometry by labeling cells with Annexin V-FITC. The expression of the relevant proteins was examined by Western blotting. The data revealed that KRAS-mutant cells were more sensitive to quercetin-induced apoptosis than wild-type cells. Caspase activation was involved in quercetin-induced apoptosis. In addition, quercetin selectively activated the c-Jun N-terminal kinase (JNK) pathway in KRAS-mutant cells, while inhibition of phospho-JNK by SP600125 blocked quercetin-induced apoptosis. The results of the present study suggest that treatment with quercetin, a common flavonoid in plants, is potentially a useful strategy for the treatment of CRCs carrying KRAS mutations.