Antileukemic activity of the combination of ionizing radiation with valproic acid in promyelocytic leukemia cells HL-60.
Valproic acid (VA) possesses anticonvulsant as well as anticancer properties of histondeacetylases inhibitor. Incubation of human promyelocytic leukemia cells HL-60 with VA leads to acetylation of nuclear histones H3 and H4. Using 2 mmol/l concentration we proved the expression of protein p21, which relates to the arrest of cell proliferation and decrease in number of cells in S phase of cell cycle. Treatment of HL-60 cells with VA causes their differentiation, proved as increase in CD11b expression. The most widely used method in cancer treatment is radiotherapy. 24 hours after irradiation by the therapeutical dose of 2 Gy, 56% of HL-60 cells are accumulated in G2 phase of cell cycle. VA had no influence on this accumulation, but 24 h-long pretreatment of cells with 1 mmol/l VA provoked higher decrease in cell number in S phase (18%) comparing with only irradiated cells (25%). The results of our work show that VA posseses radiosensitizing properties when applied 24 hours prior to irradiation and that during parallel long-term action of VA and IR the cells undergo differentiation and faster apoptosis induction. Radiosensitizing effect of VA is not caused by abrogation of G2/M cell cycle arrest, but VA induces p21 and leads to differentiation of HL-60 cells.
Rezacova
M
M
Department of Medical Biochemistry, Faculty of Medicine in Hradec Králové, Charles University in Prague, Faculty Hospital Hradec Králové, Czech Republic. rezacovam@lfhk.cuni.cz
Zaskodova
D
D
Vavrova
J
J
Vokurkova
D
D
Tichy
A
A
D000107:Acetylation; D017209:Apoptosis; D002453:Cell Cycle; D049109:Cell Proliferation; D003131:Combined Modality Therapy; D018922:HL-60 Cells; D006657:Histones / Q000378:metabolism; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy* / Q000532:radiotherapy*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D014635:Valproic Acid / Q000494:pharmacology*
D006657:Histones; D011838:Radiation-Sensitizing Agents; D014635:Valproic Acid