Different effects of two cyclic chalcone analogues on cell cycle of Jurkat T cells

Zsuzsanna Rozmer, Timea Berki, Pál Perjési

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

It has been previously shown that the cyclic chalcone analogues E-2-(4′-methoxybenzylidene)- (2) and E-2-(4′-methylbenzylidene)-1-benzusuberone (3) inhibited proliferation of various murine and human tumor cells. In order to gain new insights into the cytotoxic mechanism of the two compounds detection of apoptosis and necrosis of Jurkat T cells exposed to 2 and 3 were performed by flow cytometry using the Annexin V-FITC and propidium iodide double staining method. Analysis of the DNA histograms at 8, 24 and 48 h exposure times showed that near equitoxic doses of 2 and 3 had different effects on the cell cycle of the exposed cells. The immediate (8 h) effect of 2 was a remarkable decrease of cells in the G0/G1 phase and increase in the G2/M phase. This effect could also be seen in the histogram of cells at the 24 h time point. On the contrary, such an effect of 3 could not be observed. At the 24 and 48 h time points accumulation of sub-G0 (apoptotic and necrotic) and hyperdiploid cells could be detected after both treatments. Incubation of 2 and 3 with reduced glutathione under cell-free conditions indicated spontaneous conjugation (non-redox) reaction at pH 7.4 and pH 9.0. Analyzing the mechanism of action the total thiol content of the cells exposed to compounds 2 and 3 was determined. Compound 2 showed to reduce the total cellular thiol level both under nutrient-free and nutrient-supplemented conditions. Under the latter conditions an increase of the total thiol level of the cells exposed to 3 for 4 h could be observed. The different effect of the two compounds on the cellular thiol status might contribute to the different tumor cytotoxicity of the cyclic chalcone analogues 2 and 3. Investigation of antioxidant capacity of the compounds by monitoring time course of the Fenton-reaction initiated in vitro degradation of 2-deoxyribose indicated that both compounds displayed hydroxyl radical scavenger activity. The experiments provide further details of dual - cytotoxic and cytoprotective (chemopreventive) - effects of the compounds.

Original languageEnglish
Pages (from-to)1354-1362
Number of pages9
JournalToxicology in Vitro
Volume20
Issue number8
DOIs
Publication statusPublished - Dec 1 2006

    Fingerprint

Keywords

  • Apoptosis
  • Cyclic chalcone analogues
  • Flow cytometry
  • G/M arrest
  • Hyperdiploidity
  • Jurkat T cells

ASJC Scopus subject areas

  • Toxicology

Cite this