RESUMEN
Multidrug resistance (MDR) is one of the major obstacles in cancer chemotherapy. Our previous study has shown that icariin could reverse MDR in MG-63 doxorubicin-resistant (MG-63/DOX) cells. It is reported that icariin is usually metabolized to icariside II and icaritin. Herein, we investigated the effects of icariin, icariside II, and icaritin (ICT) on reversing MDR in MG-63/DOX cells. Among these compounds, ICT exhibited strongest effect and showed no obvious cytotoxicity effect on both MG-63 and MG-63/DOX cells ranging from 1 to 10 µmol·L-1. Furthermore, ICT increased accumulation of rhodamine 123 and 6-carboxyfluorescein diacetate and enhanced DOX-induced apoptosis in MG-63/DOX cells in a dose-dependent manner. Further studies demonstrated that ICT decreased the mRNA and protein levels of multidrug resistance protein 1 (MDR1) and multidrug resistance-associated protein 1 (MRP1). We also verified that blockade of STAT3 phosphorylation was involved in the reversal effect of multidrug resistance in MG-63/DOX cells. Taken together, these results indicated that ICT may be a potential candidate in chemotherapy for osteosarcoma.
Asunto(s)
Antineoplásicos/farmacología , Resistencia a Múltiples Medicamentos/efectos de los fármacos , Resistencia a Antineoplásicos/efectos de los fármacos , Flavonoides/farmacología , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/efectos de los fármacos , Factor de Transcripción STAT3/metabolismo , Subfamilia B de Transportador de Casetes de Unión a ATP/efectos de los fármacos , Subfamilia B de Transportador de Casetes de Unión a ATP/genética , Subfamilia B de Transportador de Casetes de Unión a ATP/metabolismo , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Doxorrubicina/metabolismo , Doxorrubicina/farmacología , Doxorrubicina/toxicidad , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/genética , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/metabolismo , Osteosarcoma/tratamiento farmacológico , Osteosarcoma/metabolismo , Osteosarcoma/patología , Fosforilación/efectos de los fármacos , Rodamina 123/metabolismo , Factor de Transcripción STAT3/antagonistas & inhibidores , Triterpenos/farmacologíaRESUMEN
AIM: To investigate the chemical constituents from Picria fel-terrae Lour. METHODS: Column chromatography techniques were used to isolate the chemical constituents, physico-chemical constants and spectroscopic analysis were employed for structural elucidation. Results Two triterpenoids named picfeltarraenone I (1) and picfeltarraenin XI (2) were isolated, and their structures were established to be 3,11,22-trioxo-16alpha-hydroxy-(20S,24)-epoxy-cucurbit-5,23-diene (1) and 3,11,22-trioxo-16alpha-hydroxy-(20S,24)-epoxy-cucurbit-5, 23-diene-2beta-O-beta-D-glucopyranoside (2), respectively. CONCLUSION: Compound 2 is a new compound, the 13CNMR data of compound 1 is reported for the first