title: 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).
authors.affiliation: a Molecular Carcinogenesis and Chemoprevention Division, Department of Medical Elementology and Toxicology, Faculty of Science , Jamia Hamdard (Hamdard University) , New Delhi , India.
authors.forename: Abdul Quaiyoom
authors.initials: AQ
authors.lastname: Khan
authors.forename: Rehan
authors.initials: R
authors.lastname: Khan
authors.forename: Mir
authors.initials: M
authors.lastname: Tahir
authors.forename: Muneeb U
authors.initials: MU
authors.lastname: Rehman
authors.forename: Abdul
authors.initials: A
authors.lastname: Lateef
authors.forename: Farrah
authors.initials: F
authors.lastname: Ali
authors.forename: Oday O
authors.initials: OO
authors.lastname: Hamiza
authors.forename: Syed Kazim
authors.initials: SK
authors.lastname: Hasan
authors.forename: Sarwat
authors.initials: S
authors.lastname: Sultana
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology*; D063646:Carcinogenesis / Q000187:drug effects* / Q000378:metabolism; D002374:Catalase / Q000235:genetics / Q000378:metabolism; D002471:Cell Transformation, Neoplastic / Q000187:drug effects* / Q000378:metabolism; D018890:Chemoprevention; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D005260:Female; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy*; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D051379:Mice; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D000077385:Silybin; D012838:Silymarin / Q000494:pharmacology*; D012867:Skin / Q000187:drug effects / Q000473:pathology; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D053583:Interleukin-1beta; D015850:Interleukin-6; D016328:NF-kappa B; D012838:Silymarin; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D009569:Nitric Oxide; D000077385:Silybin; D005954:Glucosephosphate Dehydrogenase; D002374:Catalase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D013755:Tetradecanoylphorbol Acetate