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Fomes fomentarius and Tricholoma anatolicum (Agaricomycetes) Extracts Exhibit Significant Multiple Drug-Resistant
Hasan Hüseyin Doğan1, Meltem Demirel Kars2, Özdem Özdemir1
1Biology Department, Science Faculty, Selçuk University, Campus, Konya, Turkey.
Abstract:
Multiple drug resistance is one of the main problems that hinder successful cancer chemotherapy. Investigations on the development of effective chemotherapeutic agents and drug resistance inhibitors motivate studies on the effects of natural compounds on drug-resistant cancer cells. For this purpose, aqueous, methanol, and ethanol extracts of Fomes fomentarius and Tricholoma anatolicum were prepared. The extracts were evaluated to assess their anticancer and multiple drug resistance modulation activities. Cytotoxic effects of F. fomentarius and T. anatolicum extracts on paclitaxel and vincristine resistant P-glycoprotein over-expressing MCF-7 cell lines were investigated by cytotoxicity test (XTT). P-glycoprotein reversing ability and MDR modulation effects of the extracts were determined by flow cytometry through Rhodamine 123 exclusion assay. Furthermore, 11 phenolic compounds in the extracts were characterized by HPLC. As a result of the cytotoxicity assay, IC50 values of the extracts for MCF-7/Vinc were between 1.08 and 1.80 mg/mL, and IC50 values for MCF-7/Pac were found between 1.11 and 2.83 mg/mL. Strikingly, methanol extract of F. fomentarius and ethanol extract of T. anatolicum have potential value to become MDR reversing agents for drug-resistant breast cancer cells.
Insights
Natural mushroom extracts from Fomes fomentarius and Tricholoma anatolicum show promise in overcoming multiple drug resistance (MDR) in breast cancer cells. These extracts may help reverse resistance to common chemotherapy drugs like paclitaxel and vincristine.
Area of Science:
- Pharmacology
- Natural Products Chemistry
- Oncology
Background:
- Multiple drug resistance (MDR) significantly limits the efficacy of cancer chemotherapy.
- P-glycoprotein (P-gp) overexpression is a primary mechanism contributing to MDR in various cancers.
- Natural compounds are being investigated for their potential to overcome MDR and enhance chemotherapeutic outcomes.
Purpose of the Study:
- To evaluate the anticancer and MDR modulation activities of Fomes fomentarius and Tricholoma anatolicum extracts.
- To assess the potential of these mushroom extracts in reversing P-glycoprotein-mediated drug resistance.
- To identify phenolic compounds within the extracts that may contribute to their observed activities.
Main Methods:
- Preparation of aqueous, methanol, and ethanol extracts from F. fomentarius and T. anatolicum.
- Cytotoxicity assessment using the XTT assay on paclitaxel and vincristine-resistant MCF-7 cell lines (MCF-7/Pac and MCF-7/Vinc).
- Flow cytometry analysis using Rhodamine 123 exclusion assay to determine P-glycoprotein reversing ability and MDR modulation effects.
- High-Performance Liquid Chromatography (HPLC) for characterizing phenolic compounds.
Main Results:
- The extracts exhibited cytotoxic effects against drug-resistant MCF-7 cell lines, with IC50 values ranging from 1.08 to 2.83 mg/mL.
- Methanol extract of F. fomentarius and ethanol extract of T. anatolicum demonstrated significant potential as MDR reversing agents.
- HPLC analysis identified 11 phenolic compounds in the tested extracts.
Conclusions:
- Fomes fomentarius and Tricholoma anatolicum extracts possess cytotoxic and MDR-modulating properties against drug-resistant breast cancer cells.
- Specific extracts, notably the methanol extract of F. fomentarius and ethanol extract of T. anatolicum, show promise for developing novel MDR reversal strategies.
- Further research into these natural compounds could lead to improved therapeutic approaches for overcoming chemotherapy resistance in breast cancer.
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