Rutin Inhibits Hepatic and Pancreatic Cancer Cell Proliferation by Inhibiting CYP3A4 and GST

Abstract

Background: Digestive cancer is among the major causes of mortality and morbidity worldwide. Rutin, a bioactive secondary metabolite belonging to flavonoids and distributed in many fruits and vegetables has shown anti-proliferative, anti-cancer, and neuroprotective activities. In this study, the antiproliferative, antioxidant and apoptotic activities of rutin on hepatic and pancreatic cancer cell lines were investigated. Materials and Methods: The effect on cellular viability was monitored by SRB assay. Increasing activity of caspases (3/7) was used as an indicator of apoptosis. Additionally, the anti-inflammatory and antioxidant activities of rutin were evaluated after measuring amount of prostaglandin E2 (PGE2) produced and through DPPH free radical scavenging assays, respectively. Moreover, the inhibitory effect on both CYP3A4 and GST enzymes has also been evaluated. Results: According to the data presented here, rutin has anti-proliferative effect and raises the number of caspases 3/7 in investigated cell lines. Conclusion: HepG-2 cells showed the highest cellular growth inhibition, followed by BxPC-3, Huh-7, MiaPaCa-2, Suit-2, and the normal cell line HPDE. Rutin also inhibited the cyctochrome P450 enzyme (CYP450 3A4) and glutatihione-S-transferase activity, with dose-dependent inhibition. Furthermore, suppression of PGE2 synthesis in BxPC-3 cells supported rutin's anti-inflammatory action (high COX-2 expression).