| Título: | Enhancement of paclitaxel transport and cytotoxicity by 7,3’,4’-trimethoxyflavone, a P-glycoprotein inhibitor |
| Autores: |
Jeong, Ju-Mi; Research Center for Resistant Cells and Department of Pharmacology, Chosun University Medical School, Gwangju 501-759, Republic of Korea Choi, Cheol-Hee; Dept of Pharmaoclogy, Chosun Univ Med Sch |
| Fecha: | 2007-10-29 |
| Publicador: | Journal of Pharmacy and Pharmaceutical Sciences |
| Fuente: |
 |
| Tipo: |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion |
| Tema: | No aplica |
| Descripción: | Purpose.: Paclitaxel has problems with respect to bioavailability and resistance. The aim of this study was to select a P-glycoprotein (Pgp)- inhibitory flavonoid to enhance paclitaxel bioavailability in the Caco-2 cell monolayer. Methods. Cytotoxicity and chemosensitization were determined using MTT assay. Paclitaxel transport was examined in the Caco-2 cell monolayer, which mimics the intestinal barrier. Paclitaxel concentrations were quantitated by HPLC assay using the internal standard method. Results. Chemosensitizing indeces of 7,3’,4’-trimethoxyflavone (TMF) and verapamil was > 333 and 152, respectively. The basolateral (BL)- to-apical (AP) transport of paclitaxel was more than 10-fold greater than its AP-to-BL transport. TMF and verapamil increased the AP-to-BL transport of paclitaxel but decreased its BL-to-AP transport in a concentration-dependent manner. The net absorptive effect of 50 ?M TMF on paclitaxel transport was comparable to that of 50 ?M verapamil. In addition, AP loading of TMF increased the paclitaxel sensitivity of paclitaxelresistant SK-MES-1/PT4000 cells overexpressing Pgp on the BL side. Conclusions. These results indicate that TMF with low toxicity can be used as an enhancer of oral paclitaxel bioavailability and as a Pgp inhibitor. |
| Idioma: | Inglés |
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