ISSN:
1432-0843
Keywords:
Key words Chalcones
;
Quercetin
;
MDR Cancer cell lines
;
AbbreviationsCMFDA Chloro-methyl-fluorescein diacetate
;
DCHFDA Dichloro-dihydro-fluorescein diacetate
;
MDR Multidrug resistance
;
P-gp P-Glycoprotein
;
Rh123 Rhodamine 123
;
ROS Reactive oxygen species
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract Purpose: Among flavonoids, chalcones have been identified as interesting compounds having chemopreventive and antitumor properties. We studied a panel of newly developed chalcone analogues (S1–S10) using MDA-MB 231 and MCF-7 ADRr breast cancer cells and the T-leukemic Jurkat cell line. Quercetin was used as the reference compound. Methods: Antiproliferative activity was evaluated by cell counts performed after 72 h of exposure to the drugs. DNA analysis and redox activity were evaluated using flow cytometry. Apoptosis was assessed by morphological analysis, using YOYO-1 as DNA dye; p-glycoprotein function was ascertained by quantitating the efflux of rhodamine 123. Results: All cells were sensitive to chalcone analogues yielding IC50 in micromolar concentrations with the following order regardless of the multidrug resistance (MDR) status: S1 〉 S2 〉 quercetin. S1 and S2, the most active compounds, were selected to evaluate their effect on the cell cycle, apoptosis, redox activity, and modulation of the p-glycoprotein function. No significant perturbation in cell cycle was seen with concentration up to 1 μM after 24 h. After 72 h a slight increase in G2/M block and DNA fragmentation occurred at 10 μM. Morphological analysis of apoptosis showed that chalcone analogues induced apoptosis to a higher extent than quercetin. Redox analysis demonstrated that all substances were able to increase intracellular thiol levels, which returned to baseline value after 24 h for all drugs except quercetin. Production of reactive oxygen species was essentially unaffected by all compounds. Finally, in MDR-positive MCF-7 ADRr cells chalcone analogues were unable to modulate p-glycoprotein function while quercetin was able to. Conclusions: Newly developed S1 and S2 chalcones have a different but higher antitumor activity than quercetin and could be considered as potential new anticancer drugs.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/s002800000160
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