Silibinin Inhibits Tumor Promotional Triggers and Tumorigenesis Against Chemically Induced Two-Stage Skin Carcinogenesis in Swiss Albino Mice: Possible Role of Oxidative Stress and Inflammation

Abstract

Silibinin is a major bioactive flavonolignan present in milk thistle (Silybum marianum) that possesses antioxidant, antiinflammatory, and anticarcinogenic activity. However, the precise underlying mechanism remains to be elucidated. The present study was designed to investigate underlying molecular mechanism for antitumorigenic potential of silibinin against chemically induced skin tumorigenesis in Swiss albino mice. In light of the important role of nuclear factor-kappaB (NF-κB), cyclooxygenase-2 (COX-2), iNOS, proinflammatory cytokines, vascular endothelial growth factor, and oxidative stress in carcinogenesis, chemopreventive efficacy of silibinin against 7, 12-dimethylbenz[a]anthracene/12-O-tetradecanoylphorbol-13-acetate-induced 2-stage skin carcinogenesis was studied in terms of cytoprotective enzymes activity, lipid peroxidation, inflammatory responses, and the expression of various molecular marker in skin tissue. We found that topical application of silibinin at the dose of 9 mg/mouse effectively suppressed oxidative stress and deregulated activation of inflammatory mediators and tumorigenesis. Thus, findings of the present study suggest that the chemopreventive effect of silibinin is associated with upregulation of endogenous cytoprotective machinery and down regulation of inflammatory mediators (nitric oxide, tumor necrosis factor-α, interleukin-6, interleukin -1β, COX-2, iNOS, and NF-κB).