title: In vitro evaluation of newly developed chalcone analogues in human cancer cells.
abstract: OBJECTIVE
  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 microM after 24 h. After 72 h a slight increase in G2/M block and DNA fragmentation occurred at 10 microM. 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.
authors.affiliation: Department of Obstetrics and Gynecology, Catholic University of the Sacred Heart, Rome, Italy.
authors.forename: R
authors.initials: R
authors.lastname: De Vincenzo
authors.forename: C
authors.initials: C
authors.lastname: Ferlini
authors.forename: M
authors.initials: M
authors.lastname: Distefano
authors.forename: C
authors.initials: C
authors.lastname: Gaggini
authors.forename: A
authors.initials: A
authors.lastname: Riva
authors.forename: E
authors.initials: E
authors.lastname: Bombardelli
authors.forename: P
authors.initials: P
authors.lastname: Morazzoni
authors.forename: P
authors.initials: P
authors.lastname: Valenti
authors.forename: F
authors.initials: F
authors.lastname: Belluti
authors.forename: F O
authors.initials: FO
authors.lastname: Ranelletti
authors.forename: S
authors.initials: S
authors.lastname: Mancuso
authors.forename: G
authors.initials: G
authors.lastname: Scambia
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000096:biosynthesis; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002599:Chalcone / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004273:DNA, Neoplasm / Q000187:drug effects / Q000235:genetics; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D007887:Fabaceae / Q000737:chemistry; D019450:Genes, MDR / Q000235:genetics; D006801:Humans; D019169:Jurkat Cells / Q000187:drug effects; D010946:Plants, Medicinal; D017382:Reactive Oxygen Species / Q000378:metabolism; D020112:Rhodamine 123; D014407:Tumor Cells, Cultured
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D000972:Antineoplastic Agents, Phytogenic; D004273:DNA, Neoplasm; D017382:Reactive Oxygen Species; D020112:Rhodamine 123; D002599:Chalcone