Fermented wheat germ extract inhibits glycolysis/pentose cycle enzymes and induces apoptosis through poly(ADP-ribose) polymerase activation in Jurkat T-cell leukemia tumor cells
| Autor: | Joan Boren, Neus Agell, Begoña Comı́n-Anduix, Josep J. Centelles, Josep Lluís Torres, Silvia Marin, Laszlo G. Boros, Sara Bassilian, Carles Callol-Massot, Marta Cascante |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Leukemia
T-Cell Poly ADP ribose polymerase T cells Apoptosis Pentose phosphate pathway Biology Glucosephosphate Dehydrogenase Biochemistry Jurkat cells Gas Chromatography-Mass Spectrometry Pentose Phosphate Pathway chemistry.chemical_compound Jurkat Cells Hexokinase Ribose Humans Enzyme Inhibitors Molecular Biology Triticum Carbon Isotopes Leukemia L-Lactate Dehydrogenase Cell growth Plant Extracts Fermented Wheat Germ Extract Leucèmia Cell Biology Cell cycle Molecular biology Enzyme Activation chemistry Cèl·lules T Fermentation Lactates Poly(ADP-ribose) Polymerases Transketolase Glycolysis |
| Zdroj: | Dipòsit Digital de la UB Universidad de Barcelona Digital.CSIC. Repositorio Institucional del CSIC instname |
| ISSN: | 0021-9258 |
| Popis: | 7 pages, 6 figures, 2 tables.-- PMID: 12351627 [PubMed]. The fermented extract of wheat germ, trade name Avemar, is a complex mixture of biologically active molecules with potent anti-metastatic activities in various human malignancies. Here we report the effect of Avemar on Jurkat leukemia cell viability, proliferation, cell cycle distribution, apoptosis, and the activity of key glycolytic/pentose cycle enzymes that control carbon flow for nucleic acid synthesis. The cytotoxic IC(50) concentration of Avemar for Jurkat tumor cells is 0.2 mg/ml, and increasing doses of the crude powder inhibit Jurkat cell proliferation in a dose-dependent fashion. At concentrations higher than 0.2 mg/ml, Avemar inhibits cell growth by more than 50% (72 h of incubation), which is preceded by the appearance of a sub-G(1) peak on flow histograms at 48 h. Laser scanning cytometry of propidium iodide- and annexin V-stained cells indicated that the growth-inhibiting effect of Avemar was consistent with a strong induction of apoptosis. Inhibition by benzyloxycarbonyl-Val-Ala-Asp fluoromethyl ketone of apoptosis but increased proteolysis of poly(ADP-ribose) indicate caspases mediate the cellular effects of Avemar. Activities of glucose-6-phosphate dehydrogenase and transketolase were inhibited in a dose-dependent fashion, which correlated with decreased (13)C incorporation and pentose cycle substrate flow into RNA ribose. This decrease in pentose cycle enzyme activities and carbon flow toward nucleic acid precursor synthesis provide the mechanistic understanding of the cell growth-controlling and apoptosis-inducing effects of fermented wheat germ. Avemar exhibits about a 50-fold higher IC(50) (10.02 mg/ml) for peripheral blood lymphocytes to induce a biological response, which provides the broad therapeutic window for this supplemental cancer treatment modality with no toxic effects. This work was supported by Grants PPQ 2000-0688-CO5-03 and PPQ 2000-0688-C05-04 from the Spanish government, by NATO Collaborative Grant LST.CLG.976283, by Grant PHS M01-RR00425 from the General Clinical Research Unit, and by Grant P01-CA42710 of the UCLA Clinical Nutrition Research Unit Stable Isotope Core. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|