Rutin Suppresses DMBA Carcinogenesis in the Breast Through Modulating IL-6/NF-κB, SRC1/HSP90 and ER-α

Abstract

Rutin dietary supplements may offer pharmacological benefits as anticancer and antiinflammatory properties. This study aimed to investigate the inhibitory and protective effect of rutin on signaling pathways of mammary gland carcinogenesis expermintally induced in female rats by 7,12-di-methyl benz (a) anthracene (DMBA). Results showed that rutin administration ameliorated DMBA toxicity and carcinogic effect on kidney and liver revealed by a significant decrease of urea and creatinine levels, and the activity of the liver enzymes alanine aminotransferase (ALT) and alkaline phosphatase (ALP). The antioxidant state indicated by the total antioxidant capacity (TAC) was significantly increased accompanied by a reduction in the inflammatory markers of interleukin-1β (IL-1B), interleukin-6 (IL-6), and tumor necrosis factor (TNF-α) with induction of apoptosis indicated by a significant increase in caspase-3 level. Rutin significantly reduced the levels of the tumor markers carcinoma antigen 15-3 (CA 15-3) and proto-oncogene tyrosine-protein kinase Src1 (Src1). along with downregulation of nuclear factor-kB (NF-κB), heat shock protein 90 (HSP 90), and inducible nitric oxide synthase (iNOS) gene expression. The present study demonstrated the beneficial anticancer activity of rutin as a protective and therapeutic agent. Rutin induces its antitumor activity through elevation of the antioxidant state, inhibition of inflammatory cytokines, downregulation of oncogenes expression, and stimulation of apoptosis.