Journal
CELL BIOLOGY INTERNATIONAL
Volume 43, Issue 2, Pages 117-124Publisher
WILEY
DOI: 10.1002/cbin.11055
Keywords
apoptosis; colorectal cancer; JNK; KRAS mutation; quercetin
Categories
Funding
- Natural Science Foundation of China [81471551, 81571861]
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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.
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