RESUMEN
Biotransformation by the endophytes of certain plants changes various compounds, and this 'green' chemistry becomes increasingly important for finding new products with pharmacological activity. In this study, polyphyllin VII (PPL7) was biotransformed by endophytes from the medicinal plant Paris polyphylla Smith, var. yunnanensis. This produced a new compound, ZH-2, with pharmacological activity in vitro and in vivo. ZH-2 was more potent than PPL7 in selectively killing more chemoresistant than chemosensitive breast cancer cells. ZH-2 also re-sensitized chemoresistant breast cancer cells, as evidenced by the improved anti-cancer activity of commonly-used chemotherapeutic agent in vitro, in vivo, and in clinical samples. This anti-chemoresistance effect of ZH-2 was associated with inhibiting the epithelial-mesenchymal transition (EMT) pathway. Taken together, our findings are the first one to link biotransformation with a biomedicine. The results provide insights into developing new pharmacologically-active agents via biotransformation by endophytes.
Asunto(s)
Antineoplásicos/farmacología , Neoplasias de la Mama/tratamiento farmacológico , Descubrimiento de Drogas/métodos , Resistencia a Antineoplásicos/efectos de los fármacos , Saponinas/metabolismo , Saponinas/farmacología , Animales , Antineoplásicos/metabolismo , Biotransformación , Neoplasias de la Mama/patología , Proliferación Celular/efectos de los fármacos , Delftia acidovorans/metabolismo , Relación Dosis-Respuesta a Droga , Endófitos/metabolismo , Transición Epitelial-Mesenquimal/efectos de los fármacos , Femenino , Tecnología Química Verde , Humanos , Liliaceae/microbiología , Células MCF-7 , Ratones Desnudos , Carga Tumoral/efectos de los fármacos , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Enzymatic synthesis of monoglycerides by glycerolysis of oil and fats in microaqueous solvent-free media was investigated by using lipase from pseudomonus fluorescens (PFL). Initial eutectic point(IEP) was substituted for melt point of oil and fats in Critical Temperature Theory. By investigating the glycerolysis under different IEP, it is showed that there is a relationship between composition of the oils and the yield of monoglycerides: Y = -0.0006 X3 + 0.0592 X2 - 0.8909 X + 26.753(13% < X < 76.5%), here X is the contents(W/W) of saturated fatty acid residue (C16 + C18) in the oils, Y is the yield of monoglycerides at 40 degrees C. The optimum isothermal reaction conditions for a system which IEP is 40 degrees C are: 40 degrees C, 3%-4.5% (W/W) water in glycerol, dosage of lipase is 500 u/g oil when the mole ratio of glycerol to oil is 2.5:1. The highest yield of monoglycerides is 81.4% in 48 h by means of programming temperature reaction.