Paclitaxel-induced FasL-independent apoptosis and slow (non-apoptotic) cell death.
Microtubule-active drugs, including paclitaxel (Taxol, PTX), cause mitotic arrest, and this can result in apoptosis. A recently study has reported that PTX mediates apoptosis by upregulating FasL in Jurkat and MDA-231 cells. In contrast to the previous report, we found that anti-FasL antibodies failed to inhibit PTX-induced apoptosis in Jurkat cells. In MDA-231 cells, neither FasL nor PTX induced apoptosis. In these cells, PTX caused slow cell death without activation of caspase-3 or -8 or PARP cleavage. Doxorubicin at cytostatic concentrations did not affect FasL-induced apoptosis but inhibited PTX-induced apoptosis in Jurkat cells. Following PTX-induced mitotic arrest Jurkat cells undergo apoptosis, whereas MDA-MB-231 cells exit mitosis and form multinucleated cells which then die in a slower non-apoptotic manner.
Blagosklonny
Mikhail V
MV
Medicine Branch, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA. M_Blagosklonny@NYMC.Edu
Robey
Robert
R
Sheikh
M Saeed
MS
Fojo
Tito
T
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D016923:Cell Death / Q000187:drug effects*; D004317:Doxorubicin / Q000494:pharmacology; D053222:Fas Ligand Protein; D006801:Humans; D008562:Membrane Glycoproteins / Q000502:physiology*; D017239:Paclitaxel / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000972:Antineoplastic Agents, Phytogenic; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D004317:Doxorubicin; D017239:Paclitaxel