Modulation of cancer cell multidrug resistance by an extract of Ficus citrifolia.
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.
Simon
P N
PN
Département de Botanique, Pharmacognosie, Homeopathie, Institut des Sciences Pharmaceutiques et Biologiques, 8 Avenue Rockefeller, 69008 Lyon, France.
Chaboud
A
A
Darbour
N
N
Di Pietro
A
A
Dumontet
C
C
Lurel
F
F
Raynaud
J
J
Barron
D
D
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D002455:Cell Division; D005591:Chemical Fractionation; D003630:Daunorubicin / Q000378:metabolism; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005453:Fluorescence; D006801:Humans; D007424:Intracellular Fluid / Q000378:metabolism; D020014:K562 Cells; D010936:Plant Extracts / Q000494:pharmacology; D019685:Rosales / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014747:Vinblastine / Q000378:metabolism
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000972:Antineoplastic Agents, Phytogenic; D010936:Plant Extracts; D014747:Vinblastine; D003630:Daunorubicin