Modulation of cancer cell multidrug resistance by an extract of Ficus citrifolia.
Cuvinte cheie
Abstract
Multidrug resistance due to P-glycoprotein is a serious impediment to successful chemotherapy of cancer. Previous studies have shown that natural compounds such as prenyl flavonoids are able to modulate the multidrug resistance phenotype of P-glycoprotein-positive cancer cells. A fraction from the dichloromethane extract of a common Guadalupe Ficus, Ficus citrifolia was studied for its direct interaction with the purified C-terminal cytosolic domain of P-glycoprotein, and for its induced accumulation and cytotoxicity of vinblastine and daunomycin in two model cell lines overexpressing P-glycoprotein, namely K562/R7 and MESSA/Dx5. The fraction bound with high affinity to P-glycoprotein C-terminal cytosolic domain and was as efficient as cyclosporin A to increase intracellular accumulation of daunomycin in K562/R7 leukemic cells. Moreover, the fraction markedly enhanced the cytotoxic effect of vinblastine on the growth of MESSA/Dx5 cells. These results suggest that Ficus citrifolia possesses important therapeutic potential for improving the efficacy of cancer chemotherapy.