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Modulation of cancer cell multidrug resistance by an extract of Ficus citrifolia
P N Simon1, A Chaboud, N Darbour
1Département de Botanique, Pharmacognosie, Homeopathie, Institut des Sciences Pharmaceutiques et Biologiques, 8 Avenue Rockefeller, 69008 Lyon, France.
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.
Insights
A Ficus citrifolia extract effectively combats cancer multidrug resistance by interacting with P-glycoprotein. This natural compound enhances chemotherapy drug efficacy, showing therapeutic potential against resistant cancers.
Area of Science:
- Pharmacology
- Natural Products Chemistry
- Cancer Biology
Background:
- Multidrug resistance (MDR) mediated by P-glycoprotein (P-gp) significantly limits cancer chemotherapy effectiveness.
- Natural compounds, including prenyl flavonoids, have demonstrated potential in modulating P-gp-mediated MDR.
- Investigating natural sources for MDR modulators is crucial for developing novel cancer treatment strategies.
Purpose of the Study:
- To evaluate the potential of a Ficus citrifolia extract in overcoming P-glycoprotein-mediated multidrug resistance.
- To assess the direct interaction of the Ficus citrifolia fraction with the P-glycoprotein C-terminal cytosolic domain.
- To determine the effect of the extract on the intracellular accumulation and cytotoxicity of chemotherapy drugs in P-gp-overexpressing cancer cells.
Main Methods:
- Preparation of a dichloromethane extract fraction from Ficus citrifolia.
- Assessing the binding affinity of the fraction to the purified P-glycoprotein C-terminal cytosolic domain.
- Evaluating the intracellular accumulation of daunomycin in K562/R7 cells treated with the fraction.
- Measuring the enhancement of vinblastine cytotoxicity in MESSA/Dx5 cells exposed to the fraction.
Main Results:
- The Ficus citrifolia fraction exhibited high-affinity binding to the P-glycoprotein C-terminal cytosolic domain.
- The extract fraction demonstrated efficiency comparable to cyclosporin A in increasing intracellular daunomycin accumulation.
- A significant enhancement of vinblastine's cytotoxic effect was observed in P-gp-overexpressing MESSA/Dx5 cells.
Conclusions:
- Ficus citrifolia extract contains compounds that directly interact with and modulate P-glycoprotein activity.
- This natural extract shows promise as an adjuvant therapy to improve the efficacy of existing cancer chemotherapeutics.
- Ficus citrifolia represents a potential therapeutic resource for overcoming multidrug resistance in cancer treatment.
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