Quercetin induces apoptosis and enhances gemcitabine therapeutic efficacy against gemcitabine-resistant cancer cells

Quercetin, an abundant flavonoid found in various fruits and vegetables, displays multiple biological activities, including anticancer effects. Therefore, quercetin is receiving increasing attention as a potential adjuvant anticancer treatment. Gemcitabine (GEM) resistance is a major issue for clinicians and patients with advanced cancers, making it crucial to determine ways to bolster its effects. In this study, we explored the anticancer effects and mechanistic actions of quercetin in GEM-resistant cancer cells. Pancreatic cancer (BxPC-3, PANC-1) and hepatocellular carcinoma (HepG2, Huh-7) cell lines were studied. Proliferation assays showed that quercetin had cytotoxic effects on GEM-resistant cell lines (HepG2 and PANC-1), and flow cytometric analysis indicated a significant pro-apoptotic effect on these cell lines. GEM treatment, in combination with quercetin, resulted in increased anticancer effects compared with GEM alone. Quercetin led to S phase arrest in GEM-resistant cell lines, and western blot analysis revealed tumour protein p53 upregulation and cyclin D1 downregulation. This study provides mechanistic insight into the anticancer effects of quercetin and suggests that quercetin adjuvant treatment may benefit patients who are resistant to GEM therapy.