Paclitaxel induces programmed cell death in MDA-MB-468 human breast cancer cells

Diane E. McCloskey, Scott H Kaufmann, Laura J. Prestigiacomo, Nancy E. Davidson

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

The ability of paclitaxel, one of the most active chemotherapeutic agents against breast cancer, to induce programmed cell death in hormone-independent MDA-MB-468 human breast cancer cells was assessed. Treatment of MDA-MB-468 cells led to growth inhibition, high-molecular-weight and oligonucleosomal DNA fragmentation, and apoptosis-associated morphological changes after either 3- or 24-h exposure to paclitaxel concentrations ≥10 nM. Additionally, cleavage products of poly(ADP-ribose) polymerase and lamin B1, two proteins that are cleaved early in the execution phase of programmed cell death, were detected. Quantitative studies indicated that exposure to paclitaxel for 24 h resulted in more DNA fragmentation than did 3-h exposure. Rapid induction of the early-response gene c-jun but not c-myc was associated with paclitaxel treatment. The ability of paclitaxel to induce high-molecular-weight DNA fragmentation and apoptosis-associated morphological changes in three other breast cancer cell lines was also established. These data suggest that paclitaxel, an agent known to stabilize microtubules and prevent cell division but not to act directly on DNA, induces programmed cell death in breast cancer cells.

Original languageEnglish (US)
Pages (from-to)847-854
Number of pages8
JournalClinical Cancer Research
Volume2
Issue number5
StatePublished - May 1996

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Paclitaxel
Cell Death
Breast Neoplasms
DNA Fragmentation
Molecular Weight
jun Genes
Apoptosis
Poly(ADP-ribose) Polymerases
Microtubules
Cell Division
Hormones
Cell Line
DNA
Growth
Proteins

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

McCloskey, D. E., Kaufmann, S. H., Prestigiacomo, L. J., & Davidson, N. E. (1996). Paclitaxel induces programmed cell death in MDA-MB-468 human breast cancer cells. Clinical Cancer Research, 2(5), 847-854.

Paclitaxel induces programmed cell death in MDA-MB-468 human breast cancer cells. / McCloskey, Diane E.; Kaufmann, Scott H; Prestigiacomo, Laura J.; Davidson, Nancy E.

In: Clinical Cancer Research, Vol. 2, No. 5, 05.1996, p. 847-854.

Research output: Contribution to journalArticle

McCloskey, DE, Kaufmann, SH, Prestigiacomo, LJ & Davidson, NE 1996, 'Paclitaxel induces programmed cell death in MDA-MB-468 human breast cancer cells', Clinical Cancer Research, vol. 2, no. 5, pp. 847-854.
McCloskey, Diane E. ; Kaufmann, Scott H ; Prestigiacomo, Laura J. ; Davidson, Nancy E. / Paclitaxel induces programmed cell death in MDA-MB-468 human breast cancer cells. In: Clinical Cancer Research. 1996 ; Vol. 2, No. 5. pp. 847-854.
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