Effect of valproic acid and antiapoptotic cytokines on differentiation and apoptosis induction of human leukemia cells

Rok, strany: 2006, 65 - 79

This work compares effect of histondeacetylase inhibitor, valproic acid (VA), on proliferation, differentiation and apoptosis induction in two human leukemic cell lines: HL-60 (human promyleocytic leukemia, p53 negative) and MOLT-4 (human T-lymphocyte leukemia, p53 wild type). Incubation with VA caused decrease in percentage of cells in S phase of cell cycle. The decrease was more intensive in HL-60 cells, where the cells in S phase were absent 6 days after the beginning of incubation with VA (4 mmol/l). 3-day-long incubation of HL-60 cells with 4 mmol/l VA caused differentiation of these cells, marked by increase in CD11b and co-stimulatory/adhesion molecule CD86, and induction of a significant apoptosis. Annexin V positive cells lost the CD11b antigen. 3-day-long incubation of MOLT-4 cells with VA (1–2 mmol/l) inhibited proliferation and decreased percentage of cells in S phase of the cell cycle. 90% of MOLT-4 cells are CD7 positive. This CD7 positivity is not changed during apoptosis induction (detected as Annexin V positivity). On the other hand, CD4 marker expression decreases after incubation with 1–2 mmol/l VA, but during apoptosis induction by 4 mmol/l VA, most of the apoptotic Annexin V positive cells were also CD4 positive. Using a clonogenic survival assay EC50 for 3-day-long incubation with VA was determined. For HL-60 cells, the established EC50 was 1.84 mmol/l, for MOLT-4 cells it was 1.76 mmol/l. Ability of VA to induce differentiation in HL-60 cells thus does not affect final cell killing. However, the elimination of the cells was considerably affected by presence of hematopoietic growth factors. 14-day-long incubation of HL-60 cells with VA in conditioned medium (source of IL-3, SCF, G-CSF) caused increase in EC50 to 4 mmol/l, while in MOLT-4 cells (cultivation without conditioned medium), the EC50 decreased to 0.63 mmol/l.

ISO 690:

Řezáčová, M., Vávrová, J., Vokurková, D., Záškodová, D. 2006. Effect of valproic acid and antiapoptotic cytokines on differentiation and apoptosis induction of human leukemia cells. In General Physiology and Biophysics, vol. 25, no.1, pp. 65-79. 0231-5882.

APA:

Řezáčová, M., Vávrová, J., Vokurková, D., Záškodová, D. (2006). Effect of valproic acid and antiapoptotic cytokines on differentiation and apoptosis induction of human leukemia cells. General Physiology and Biophysics, 25(1), 65-79. 0231-5882.