Quercetin Increases Doxorubicin-Induced Apoptosis Through Oxidative DNA Damage in KATO III Gastric Cancer Cells

Abstract

Background: Gastric cancer is the most common gastrointestinal malignancy with an increasing incidence rate worldwide. Finding novel curative and preventive approaches that could target the tumor cells without affecting the normal cells and overcome drug resistance will be tremendously useful. Objectives: This study aimed to evaluate the effects of quercetin (QUE) in combination with doxorubicin (DOX) on apoptosis and its underlying mechanisms in the KATO III gastric cancer cell line. Methods: The effects of Que and DOX on cell viability were measured using an MTT assay. Western blot was used for the measurement of γH2AX protein expression. The expression levels of 8-Hydroxy-2'-deoxyguanosine were evaluated by enzyme-linked immunosorbent assay. The DCFH-DA fluorescence dye was used to detect the formation of reactive oxygen species (ROS). The activities of antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and glutathione S-transferase) were also assessed. For evaluation of apoptosis, the terminal deoxynucleotidyl transferase dUTP nick end labeling assay was used. Results: Based on the findings, QUE significantly increased the cytotoxic effects of DOX. Besides, QUE considerably increased the expression levels of γH2AX. Upon QUE treatment, ROS levels increased, and antioxidant enzyme expression levels markedly decreased. Moreover, QUE treatment resulted in the potentiation of doxorubicin-induced apoptosis in KATO III cells, compared to the cells treated with either QUE or DOX. Conclusion: Overall, co-administration of QUE and DOX enhances cytotoxicity, increases ROS levels, induces oxidative DNA damage, and decreases cellular antioxidant defense, and thereby might promise a therapeutic regimen in promoting the clinical efficacy of the treatment of patients with gastric cancer.