Hydroxydibenzoylmethane induces apoptosis through repressing ornithine decarboxylase in human promyelocytic leukemia HL-60 cells

Ornithine decarboxylase (ODC) is the rate-limiting enzyme in polyamine biosynthesis and a target for chemoprevention. Hydroxydibenzoylmethane (HDB), a derivative of dibenzoylmethane of licorice, is a promising chemopreventive agent. In this paper, we investigated whether HDB would inhibit the ODC pathway to enhance apoptosis in human promyelocytic leukemia HL-60 cells. We found ODC enzyme activity was reduced during HDB treatment. Overexpression of ODC in HL-60 parental cells could reduce HDB-induced apoptosis, which leads to loss of mitochondrial membrane potential (Deltapsim), through lessening intracellular ROS. Furthermore, ODC overexpression protected cytochrome c release and the activation of caspase-3 following HDB treatment. The results demonstrated HDB-induced apoptosis was through a mechanism of down-regulation of ODC and occurred along a ROS-dependent mitochondria-mediated pathway.

Effect of alfa-difluormethylornithine on Anastrepha fraterculus (Diptera, Tephritidae) ovary size / Efeito da alfa-difluorometilornitina nas dimensões dos ovários em Anastrepha fraterculus (Diptera, Tephritidae)

Ovarian sizes (length and width) were measured in young females of Anastrepha fraterculus (Wiedemann) (Diptera, Tephritidae) subjected or not to the inhibitor α -difluormethylornithine (α -DFMO). The most effective concentration of α -DMFO used was 50 mM and the ovarian measurements (length and width) of the treated females were smaller than those of females not treated with α -DMFO. These data may suggest some relationship between ornithine decarboxylase (ODC) and sexual maturation in A. fraterculus.

As dimensões dos ovários (comprimento e largura) foram mensuradas em fêmeas jovens da Anastrepha fraterculus (Wiedemann) (Diptera, Tephritidae) submetidas ou não ao inibidor α -difluormetilornitina (α -DFMO). A concentração mais efetiva de α -DMFO utilizada foi 50 mM e as medidas (comprimento e largura) das fêmeas tratadas com o inibidor foram menores que as fêmeas não tratadas com inibidor α -DMFO. Estes dados podem sugerir uma relação entre ornitina descarboxilase (ODC) e maturação sexual em A. fraterculus.

Effects of alpha-difluoromethylornithine on the Fas expression and apoptosis in Hep-2 cells

DFMO is an irreversible inhibitor of ornithine decarboxilase (ODC), the key enzyme in mammalian polyamine biosynthesis, and has been shown to induce apoptosis. In this paper, the relation between the effects of DFMO on the polyamine content, apoptotic index and Fas expression in HEP-2 cells was determined. Fas is a type I membrane protein with a molecular mass of 45 kDa, which mediates apoptosis. The results suggest that the treatment with the polyamine inhibitor DFMO induced the expression of the surface antigen Fas, which could be responsible for trigger apoptosis in these cells.(AU)

Effects of alpha-difluoromethylornithine on the cyclin A expression in Hep-2 cells

DFMO is an irreversible inhibitor of ornithine decarboxilase (ODC), the key enzyme in mammalian polyamine biosynthesis. The goal of this study was to determine the effects of DFMO on the expression of cyclin A at different stages of the cell cycle of Hep-2 cells. The cell cycle analysis, done by measuring the incorporation of thymidine in the cell DNA, revealed that DFMO produced a lower and constant level of that incorporation; this effect is probably due to the incapacity of the cells to culminate the phase S of the cell cycle. The expression of cyclin A increased in the phases S and G2 in control cells, almost disappearing in phase M. However, in DFMO treated cultures, the expression of cyclin A was increased in M and this effect remained still after 48 h treatment. We conclude that polyamines could exert an effect on the cyclin destruction mechanism, and the depletion caused by DFMO would alter this mechanism.(AU)