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.
Villamarín
Silvia
S
Departamento de Biología Molecular y Celular, Instituto de Biología Molecular de Barcelona, CSIC, Barcelona, Spain.
Mansilla
Sylvia
S
Ferrer-Miralles
Neus
N
Priebe
Waldemar
W
Portugal
José
J
D000782:Aneuploidy; D000903:Antibiotics, Antineoplastic / Q000378:metabolism / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D003114:Colony-Forming Units Assay; D018736:DNA Adducts; D003630:Daunorubicin / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology*; D005434:Flow Cytometry; D016195:G2 Phase / Q000187:drug effects*; D006801:Humans; D019169:Jurkat Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D018613:Microscopy, Confocal; D008858:Microscopy, Phase-Contrast; D008938:Mitosis / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects*; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D000903:Antibiotics, Antineoplastic; D018736:DNA Adducts; D016159:Tumor Suppressor Protein p53; C104426:WP 631; C020270:daunorubicin-DNA; D003630:Daunorubicin