RESUMEN
A coumestan derivative, psoralidin (1) was found to be a cytotoxic principle of the seeds of Psoralea corylifolia L. (Leguminosae) with the IC50 values of 0.3 and 0.4 microg/ml against the HT-29 (colon) and MCF-7 (breast) human cancer cell lines, respectively. A coumarin, angelicin (2) was also isolated as a marginally cytotoxic agent along with an inactive compound, psoralen (3) from the plant. The isolates 1-3 were not active against the A541 (lung) and HepG2 (liver hepatoma) cancer cell lines.
Asunto(s)
Antineoplásicos Fitogénicos/química , Plantas Medicinales/química , Psoralea/química , Animales , Antineoplásicos Fitogénicos/aislamiento & purificación , Benzofuranos/química , Benzofuranos/aislamiento & purificación , Supervivencia Celular/efectos de los fármacos , Fenómenos Químicos , Química Física , Cumarinas/química , Cumarinas/aislamiento & purificación , Ensayos de Selección de Medicamentos Antitumorales , Furocumarinas/química , Furocumarinas/aislamiento & purificación , Humanos , Indicadores y Reactivos , Espectroscopía de Resonancia Magnética , Ratas , Semillas/química , Espectrofotometría Infrarroja , Espectrofotometría Ultravioleta , Células Tumorales CultivadasRESUMEN
A variety of alkylated base adducts are repaired by 3-methyladenine DNA glycosylases, one of the base excision repair enzymes. In this study, we examined the DNA adducts induced by hepsulfam and determined whether alkylated base adducts can be substrates for bacterial and mammalian 3-methyladenine DNA glycosylases by electrophoresis methods. Hepsulfam, a synthetic analogue of busulfan, is known to alkylate DNA and form interstrand cross-links. The extent of DNA interstrand cross-links induced by hepsulfam and busulfan was found to be similar but significantly lower than that induced by chlorambucil, as measured by an agarose gel assay. The major monofunctional alkylation site of hepsulfam was observed at the N7 position of guanine, and not at the N3 position of adenine. Both compounds did not exhibit any sequence selective DNA alkylation patterns. The excision of hepsulfam-induced DNA adducts has been determined by treatment with homogeneous recombinant bacterial, rat and human 3-methyladenine DNA glycosylases and successive treatments by formamidopyrimidine-DNA glycosylase. The Escherichia coli alkA protein was shown to completely excise N7 guanine adducts, whereas mammalian 3-methyladenine DNA glycosylase failed to excise them. In addition, the cytotoxicity assay showed that E. coli mutant strains defective in the alkA gene or the uvrA gene were more sensitive to killing by hepsulfam than the wild type.