A synthetic coumarin (4-Methyl-7 hydroxy coumarin) has anti-cancer potentials against DMBA-induced skin cancer in mice
Autor: | Saili Paul, Antara Banerjee, Anisur Rahman Khuda-Bukhsh, Naoual Boujedaini, Sushil Kumar Mandal, Soumya Sundar Bhattacharyya |
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Rok vydání: | 2009 |
Předmět: |
Male
Skin Neoplasms 9 10-Dimethyl-1 2-benzanthracene Fluorescent Antibody Technique DMBA Antineoplastic Agents Mice chemistry.chemical_compound In vivo Scopoletin Animals heterocyclic compounds Carcinogen Chromosome Aberrations Pharmacology Micronucleus Tests biology Caspase 3 Cytochrome c Cell Cycle Aryl hydrocarbon receptor Coumarin Gene Expression Regulation Neoplastic Comet assay Biochemistry chemistry biology.protein Sperm Head Female Hymecromone DNA Damage Signal Transduction |
Zdroj: | European Journal of Pharmacology. 614:128-136 |
ISSN: | 0014-2999 |
DOI: | 10.1016/j.ejphar.2009.04.015 |
Popis: | Scopoletin, an alkaloid separated from ethanolic extract of the medicinal plant, Gelsemium sempervirens (Fam: Loganiaceae) has been reported to have anti-cancer potentials. The synthetic coumarin (4-Methyl-7 hydroxy coumarin) derived from resorcinol and ethyl aceto-acetate in presence of concentrated sulphuric acid is structurally close to scopoletin, being a coumarin derivative. Whether this synthetic compound also has anti-cancer potentials has been evaluated in vivo on DMBA (7,12-Dimethylbenz[a]anthracene) induced skin cancer in mice by analyzing results of several cytogenetic endpoints, Comet assay, and fluorescence activated cell sorting (FACS). Further, expressions of signal proteins like Aryl hydrocarbon receptor , p53, PCNA, Akt, Bcl-2, Bcl-xL, Bad, Bax, NF-kappaB Apaf, IL-6, Cytochrome-c, Caspase-3 and Caspase-9 were studied by immunoblot analysis along with histology of skin and immuno-histochemical localization of Aryl hydrocarbon receptor and PCNA in DMBA treated mice vis-a-vis carcinogen treated synthetic coumarin fed mice. Feeding of this synthetic coumarin induced positive modulations in expression of all biomarkers in DMBA administered mice, giving clues on its possible signaling pathway(s) - primarily through down-regulation of Aryl hydrocarbon receptor and PCNA and up-regulation of apoptotic proteins like Bax, Bad, Cytochrome c, Apaf, Caspase-3 and Caspase-9, resulting in an appreciable reduction in growth of papilloma in mice. Therefore, this synthetic coumarin shows promise for use in cancer therapy, particularly in skin cancer. |
Databáze: | OpenAIRE |
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