Growth inhibition and apoptosis induced by 2 phenoxymethyl-3H-quinazolin-4-one in HL-60 leukemia cells

• Дата: 2007
• Автори: Cipak, L., Repicky, A., Jantova, S.
• Формат: Стаття
• Мова: English
• Опубліковано: Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України 2007
• Назва видання: Experimental Oncology
• Теми: Original contributions
• Онлайн доступ: http://dspace.nbuv.gov.ua/handle/123456789/138951
• Назва журналу: Digital Library of Periodicals of National Academy of Sciences of Ukraine
• Цитувати: Growth inhibition and apoptosis induced by 2 phenoxymethyl-3H-quinazolin-4-one in HL-60 leukemia cells / L. Cipak, A. Repicky, S. Jantova // Experimental Oncology. — 2007. — Т. 29, № 1. — С. 13-17. — Бібліогр.: 21 назв. — англ.

Aim: The aim of the study was to investigate anticancer activity of newly synthesized 2-phenoxymethyl-3H-quinazolin-4-one (PMQ). Materials and Methods: Anticancer activity of PMQ was studied towards human HL-60 leukemia cells. Antiproliferative activity of PMQ was determined by direct counting of cells using trypan blue staining technique. Apoptosis and cell cycle profile changes were analysed using internucleosomal DNA fragmentation assay and flow cytometry. Activation of caspases and changes in glutathione level were monitored using colorimetric or luminiscent methods. Results: PMQ induced concentration-dependent cytotoxicity in leukemia cells, with IC50 of 10.8 ± 0.9 µM. DNA flow cytometry analysis and DNA ladder formation assay indicated that PMQ actively induced apoptosis of cells accompanied by a block of cells in G2/M phase and a marked loss of cells in G0/G1 and S phases. Additionally, the activities of caspase-3 and caspase-9 were increased significantly and a markedly increased level of oxidized glutahione was observed. Inhibition of glutahione synthesis using buthionine sulfoximine sensitized leukemia cells to PMQ, confirming the involvement of ROS in PMQ-induced apoptosis. Conclusion: The results of this study clearly demonstrate that PMQ is a promising anticancer drug showing cytostatic and apoptotic effects toward HL-60 leukemia cells mainly through mitochondrial/caspase-9 dependent pathway.