Possible Pro-oxidant and Apoptotic Effects of Quercetin and Carboplatin on SW480 Colorectal Cancer Cells
Sada Jawad Al-Nassrawi, Reyadh H. Al-Mosawi, Haider Abdul-Ridha Al-KhafajiAbstract
Background:
Quercetin is one of the most common flavonoids that show antioxidant properties and has apoptotic effect on cancer cells. Carboplatin is a widely used chemotherapeutics because of their broad-spectrum anticancer actions and unique mechanism against cancer. However, several serious adverse impacts are obstacles to its clinical application.
Objectives:
To estimate the effect of quercetin on oxidative stress, apoptosis and cytotoxicity of carboplatin in SW480 colorectal cancer cell line.
Materials and Methods:
The SW480 cancer cells and vero (nontumoral) cells were provided by the Tissue Culture Laboratory in the College of Medicine/University of Babylon. Assessment the toxic effect of quercetin was made, at different concentrations, on normal cells (vero) by using cytotoxicity (MTT) assay to determine the effective concentrations of quercetin that kill cancer cells without producing harmful effect on normal cells. Then, these concentrations of quercetin were then used in subsequent experiments in combination with IC50 of carboplatin in the treatment of SW480 cancer cells. Evaluation the cytotoxic effect of quercetin, carboplatin and the corresponding combination on SW480 cells was achieved using MTT assay. Supernatants of SW480 cells were kept at –20°C for glutathione, malondialdehyde and caspase-3 detection by enzyme-linked immunosorbent assay.
Results:
Vero cells, exposed to various concentrations of quercetin (12.5‐200) µM in 48 h period, had cell viability 81.27% and 75% at high concentration of quercetin (100 and 200 µM, respectively). However, there had no cytotoxic effect in vero cells after incubation with low concentrations of quercetin. In contrast, quercetin and carboplatin alone stopped cell proliferation and induced apoptosis by raising oxidative stress level in SW480 cells in a concentration dependent manner. Low concentration of quercetin (25 µM) attenuated cytotoxicity, oxidative stress, and apoptotic effects of carboplatin. Quercetin at 50 µM did not insignificantly change carboplatin cytotoxicity.
Conclusion:
Quercetin can antagonize the cytotoxic effect of carboplatin when used in low concentrations. Quercetin supplementation while receiving chemotherapy can result in resistance to chemotherapies.