A comparative analysis of the time-dependent antiproliferative effects of daunorubicin and WP631

Jurkat T lymphocytes were treated with daunorubicin and WP631, a daunorubicin-based DNA binding agent, in experiments aimed to analyze cellular uptake of these drugs and their effect on cell viability. WP631 was taken up more slowly than daunorubicin, but laser confocal microscopy and spectrofluorometric quantification showed that the drug accumulated in the cells. Despite the slow uptake rate, the antiproliferative capacity of WP631 (measured as IC50 after a 72-h continuous treatment) was greater than that of daunorubicin. The propensities of daunorubicin and WP631 to promote apoptosis were compared. Our results indicate that the major effect of WP631 was a G2/M arrest followed, after about 72 h of treatment, by polyploidy and mitotic (reproductive) death. In contrast, daunorubicin induced a rapid response with classic features of apoptosis.This work was financed by grants from the Spanish Ministry of Science and Technology, the Commission for the Scientific Exchange between the United States of America and Spain, and the Welch Foundation (Houston, TX, USA), and it was carried out within the framework of the Centre de Referencia en Biotecnologia (Generalitat de Catalunya). Sylvia Mansilla is recipient of a doctoral fellowship from the CIRITPeer Reviewe