We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
In vitro evaluation of newly developed chalcone analogues in human cancer cells.
- Authors
De Vincenzo, Rosa; Ferlini, Cristiano; Distefano, Mariagrazia; Gaggini, Cristiana; Riva, Antonella; Bombardelli, Ezio; Morazzoni, Paolo; Valenti, Piero; Belluti, Federica; Ranelletti, Franco Oreste; Mancuso, Salvatore; Scambia, Giovanni
- 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.
- Subjects
CHALCOCITE; CANCER cells; FATTY acids; QUERCETIN; P-glycoprotein; DRUG resistance
- Publication
Cancer Chemotherapy & Pharmacology, 2000, Vol 46, Issue 4, p305
- ISSN
0344-5704
- Publication type
Article
- DOI
10.1007/s002800000160