Anthraquinone antitumour agents, doxorubicin, pirarubicin and benzoperimidine BP1, trigger caspase-3/caspase-8-dependent apoptosis of leukaemia sensitive HL60 and resistant HL60/VINC and HL60/DOX cells

• Published in: Anti-cancer drugs Vol. 23; no. 4; pp. 380 - 392
• Main Authors: Nowak, Robert, Tarasiuk, Jolanta
• Format: Journal Article
• Language: English
• Published: England Lippincott Williams & Wilkins, Inc 01-04-2012
• Subjects: anthraquinone; Antineoplastic Agents - pharmacology; Apoptosis; Apoptosis - drug effects; ATP Binding Cassette Transporter, Sub-Family B; ATP-Binding Cassette, Sub-Family B, Member 1 - metabolism; Caspase 3 - drug effects; Caspase 3 - metabolism; Caspase 8 - drug effects; Caspase 8 - metabolism; Caspase-3; CD95 antigen; Cell cycle; Cell Line, Tumor; Doxorubicin; Doxorubicin - analogs & derivatives; Doxorubicin - pharmacology; Drug Resistance, Neoplasm; Fas antigen; fas Receptor - drug effects; Gene Expression - drug effects; Heterocyclic Compounds, 4 or More Rings - pharmacology; HL-60 Cells; Humans; Leukemia; Leukemia, Myeloid - drug therapy; Leukemia, Myeloid - metabolism; MRP protein; Multidrug resistance; P-Glycoprotein
• ISSN: 0959-4973; 1473-5741
• DOI: 10.1097/CAD.0b013e32834f8ab4

We examined the effect of selected anthraquinone antitumour agents – doxorubicin (DOX), pirarubicin (PIRA) and benzoperimidine BP1 – on inducing apoptosis of the sensitive leukaemia HL60 cell line and its multidrug resistance sublines overexpressing P-glycoprotein (HL60/VINC) and multidrug resistance-associated protein 1 (HL60/DOX). All agents used at IC50 and IC90 were able to influence the cell cycle of sensitive HL60 and resistant cells and induce apoptosis. Interestingly, it was seen that HL60/VINC cells were more susceptible to undergo caspase-3/caspase-8-dependent apoptosis induced by the studied anthraquinone compounds compared with HL60 and HL60/DOX cells. However, the examined agents did not change the expression of Fas receptors on the surface of HL60-sensitive and-resistant cells.