Taxol cytotoxicity on human leukemia cell lines is a function of their susceptibility to programmed cell death.
Taxol is the prototype of a class of antineoplastic drugs that target microtubules. It enhances tubulin-monomer polymerization and stabilizes tubulin polymers, increasing the fraction of cells in the G2 or M phase of the cell cycle. We report that treatment of HL-60 and U937 myeloid cell lines with 1-10 microM taxol induces DNA fragmentation and the appearance of morphological features consistent with the process of apoptosis. Taxol-induced apoptosis is inhibited neither by cycloheximide nor by actinomycin D and therefore appears to be independent of new protein synthesis. Taxol causes arrest in the G2 phase of the cell cycle and affects cell viability but does not induce DNA fragmentation in the K562 erythromyeloid cell line. Protein-synthesis inhibitors, colcemid, ionomycin, and starvation, known to trigger apoptosis, proved ineffective as well. These results suggest that the antineoplastic effect of taxol is mediated in susceptible cell lines by induction of the apoptotic machinery and that K562 partial resistance may depend upon the intrinsic inability of these tumor cells to undergo apoptosis.
Gangemi
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RM
Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.
Tiso
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M
Marchetti
C
C
Severi
A B
AB
Fabbi
M
M
D017209:Apoptosis / Q000187:drug effects*; D003513:Cycloheximide / Q000627:therapeutic use; D004351:Drug Resistance; D004587:Electrophoresis, Agar Gel; D005434:Flow Cytometry; D006801:Humans; D007938:Leukemia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008854:Microscopy, Electron; D017239:Paclitaxel / Q000494:pharmacology* / Q000627:therapeutic use; D013936:Thymidine / Q000378:metabolism; D013997:Time Factors; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay
D003513:Cycloheximide; D017239:Paclitaxel; D013936:Thymidine