RESUMEN
Semduramicin is an ionophore coccidiostat used in the poultry industry as a feed additive. Cross-contamination of feeds for non-target animals with semduramicin is unavoidable. However, it is not known whether undesirable residues of semduramicin may occur in food after cross-contaminated feed is administered to animals. The aim of the work was to determine the levels of semduramicin in hen eggs (yolks and albumen) and tissues (liver, muscle, spleen, gizzard, ovarian yolks and ovaries) after administration of feed contaminated with 0.27 mg kg(-1) of this coccidiostat. The residues were determined using LC-MS/MS. The distribution pattern confirmed the high lipophilicity of semduramicin. Residues were found mainly in egg yolks (28.8 µg kg(-1)), ovarian yolks (19.5 µg kg(-1)) and liver (2.57 µg kg(-1)), while hens' muscle was free from semduramicin (LOD = 0.1 µg kg(-1)). Among edible tissues, the maximum level (2 µg kg(-1)) was exceeded only in the liver.
Asunto(s)
Coccidiostáticos/farmacocinética , Huevos/análisis , Contaminación de Alimentos , Nigericina/análogos & derivados , Animales , Pollos , Coccidiostáticos/análisis , Residuos de Medicamentos/análisis , Residuos de Medicamentos/farmacocinética , Femenino , Nigericina/análisis , Nigericina/farmacocinética , Distribución TisularRESUMEN
Nasopharyngeal carcinoma (NPC) is prevalent in southern China, northern Africa, and Alaska. The prognosis for NPC patients at early stage is good, while it is poor for patients at late stages. Cancer stem cells (CSCs) have been proposed to be associated with tumor initiation, relapse and metastasis, and the poor prognosis of NPC likely results from residual CSCs after therapy. Study on the therapy targeting CSCs in NPC remains poor, though it received intensive attentions in other cancers. Here, we used NPC cell lines with high and low proportion of CSCs as models to explore the effect of nigericin, an antibiotic, on CSCs. We found that nigericin could selectively target CSCs and sensitize CSCs in NPC to the widely used clinical drug cisplatin both in vitro and in vivo. Moreover, downregulation of the polycomb group protein Bmi-1 may contribute to the inhibitory effect of nigericin on CSCs. Furthermore, by using the in vitro NPC cell models, we found that nigericin could significantly decrease the migration and invasion abilities, which are known to be associated with CSCs. Taken together, our results suggest that nigericin can selectively target CSCs in NPC, which could be a candidate CSCs targeting drug for clinical evaluation.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Neoplasias Nasofaríngeas/tratamiento farmacológico , Neoplasias Nasofaríngeas/patología , Células Madre Neoplásicas/efectos de los fármacos , Nigericina/farmacología , Animales , Antibacterianos/farmacocinética , Antibacterianos/farmacología , Carcinoma , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Movimiento Celular/fisiología , Cisplatino/administración & dosificación , Cisplatino/farmacología , Regulación hacia Abajo/efectos de los fármacos , Sinergismo Farmacológico , Humanos , Inmunohistoquímica , Ratones , Ratones Desnudos , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/metabolismo , Metástasis de la Neoplasia , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/patología , Nigericina/administración & dosificación , Nigericina/farmacocinética , Complejo Represivo Polycomb 1/metabolismo , Distribución Aleatoria , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
With addition of methyl oleate, the increased yield of antibiotic production by nigericin-producing Streptomyces hygroscopicus NRRL B-1865 also resulted in the isolation of three additional polyether antibiotics. Two of these are abierixin and epinigericin, as new antibiotics. The third antibiotic is grisorixin. The production of both abierixin (opened ring A and 30-CH2OH) and grisorixin (ring A and 30-CH3) poses the problem of the identity of the last pathway precursor of the major metabolite, nigericin (ring A and 30-CH2OH). Transformation experiments of abierixin by S. hygroscopicus gave negative results. Hydroxylation of grisorixin to nigericin by S. hygroscopicus represents the final step in nigericin biosynthesis.