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Selective cytotoxic activity and DNA damage by an epoxyalkyl galactopyranoside.
Burgos-Morón, Estefanía; Pastor, Nuria; Orta, Manuel Luis; Jiménez-Alonso, Julio José; Vega-Holm, Margarita; Vega-Pérez, José Manuel; Iglesias-Guerra, Fernando; Mateos, Santiago; López-Lázaro, Miguel; Calderón-Montaño, José Manuel.
Afiliación
  • Burgos-Morón E; Department of Pharmacology, Faculty of Pharmacy, University of Seville, Seville, Spain.
  • Pastor N; Department of Cell Biology, Faculty of Biology, University of Seville, Seville, Spain.
  • Orta ML; Department of Cell Biology, Faculty of Biology, University of Seville, Seville, Spain.
  • Jiménez-Alonso JJ; Department of Pharmacology, Faculty of Pharmacy, University of Seville, Seville, Spain.
  • Vega-Holm M; Department of Organic and Medicinal Chemistry, Faculty of Pharmacy, University of Seville, Seville, Spain.
  • Vega-Pérez JM; Department of Organic and Medicinal Chemistry, Faculty of Pharmacy, University of Seville, Seville, Spain.
  • Iglesias-Guerra F; Department of Organic and Medicinal Chemistry, Faculty of Pharmacy, University of Seville, Seville, Spain.
  • Mateos S; Department of Cell Biology, Faculty of Biology, University of Seville, Seville, Spain.
  • López-Lázaro M; Department of Pharmacology, Faculty of Pharmacy, University of Seville, Seville, Spain.
  • Calderón-Montaño JM; Department of Pharmacology, Faculty of Pharmacy, University of Seville, Seville, Spain.
Drug Dev Res ; 79(8): 426-436, 2018 12.
Article en En | MEDLINE | ID: mdl-30375672
Preclinical Research & Development Several clinically useful anticancer drugs selectively kill cancer cells by inducing DNA damage; the genomic instability and DNA repair defects of cancer cells make them more vulnerable than normal cells to the cytotoxicity of DNA-damaging agents. Because epoxide-containing compounds can induce DNA damage, we have used the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay to evaluate the selective cytotoxicity of three epoxyalkyl galactopyranosides against A549 lung cancer cells and MRC-5 lung normal cells. Compound (2S,3S)-2,3-epoxydecyl 4,6-O-(S)-benzylidene-ß-d-galactopyranoside (EDBGP) showed the highest selective anticancer activity and was selected for mechanistic studies. After observing that EDBGP induced cellular DNA damage (comet assay), we found that cells deficient in nucleotide excision repair were hypersensitive to the cytotoxicity of this compound; this suggests that EDBGP may induce bulky DNA adducts. EDBGP did not inhibit glycolysis (glucose consumption and lactate production). Pretreatment of lung cancer cells with several antioxidants did not reduce the cytotoxicity of EDBGP, thereby indicating that reactive oxygen species do not participate in the anticancer activity of this compound. Finally, EDBGP was screened against a panel of cancer cells and normal cells from several tissues, including three genetically modified skin fibroblasts with increasing degree of malignancy. Our results suggest that epoxyalkyl galactopyranosides are promising lead compounds for the development of new anticancer agents.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Daño del ADN / Citotoxinas / Galactosa Límite: Animals / Female / Humans / Male Idioma: En Revista: Drug Dev Res Año: 2018 Tipo del documento: Article País de afiliación: España Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Daño del ADN / Citotoxinas / Galactosa Límite: Animals / Female / Humans / Male Idioma: En Revista: Drug Dev Res Año: 2018 Tipo del documento: Article País de afiliación: España Pais de publicación: Estados Unidos