Caspase-7 is activated during lovastatin-induced apoptosis of the prostate cancer cell line LNCaP

Marco Marcelli, Glenn R. Cunningham, S. Joe Haidacher, Sebastian J. Padayatty, Lydia Sturgis, Carolina Kagan, Larry Denner

Research output: Contribution to journalArticle

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Abstract

The goals of this work were to establish a reproducible and effective model of apoptosis in a cell line derived from advanced prostate cancer and to study the role of the caspase family of proteases in mediating apoptosis in this system. The study involved the use of the prostate cancer cell line LNCaP. Apoptosis was induced using the hydroxymethyl glutaryl CoA reductase inhibitor, lovastatin, and was evaluated by agarose gel electrophoresis of genomic DNA, morphological criteria, and terminal deoxynucleotidyl transferase-mediated nick end labeling. Caspases were studied by catalytic activity, mRNA induction, and protein processing. Lovastatin (30 μM) was an effective inducer of apoptosis, causing changes that were evident after 48 h and essentially complete after 96-120 h of treatment. These effects were prevented by the simultaneous addition of mevalonate (300 μM) to the culture medium. Lovastatin induced a proteolytic activity that was able to cleave the enzyme poly(ADP-ribose) polymerase and the substrate Z-DEVD-AFC, which is modeled after the P1-P4 amino acids of the poly(ADP-ribose) polymerase cleavage site. Caspase-7, but not caspase-3, underwent proteolytic activation during lovastatin-induced apoptosis, an effect prevented by mevalonate. Caspase-7 was the only detected interleukin 1β converting enzyme family protease with DEVD cleavage activity that exhibited lovastatin-induced mRNA up-regulation. Again, mevalonate blocked this effect. Lovastatin-induced apoptosis also was prevented when the caspase inhibitors Z-DEVD-CH2F or Z- VAD-CH2F (100 μM) where added to the medium. These studies have identified lovastatin as a powerful inducer of apoptosis in the cell line LNCaP. Caspase activation was a necessary event for LNCaP cells to undergo apoptosis during treatment with lovastatin. Of the caspases tested, only caspase-7 underwent proteolytic activation after stimulation with lovastatin. Identification of caspase-7 as a potential mediator of lovastatin-induced apoptosis broadens our knowledge of the molecular events associated with programmed cell death in a cell line derived from prostatic epithelium.

Original languageEnglish (US)
Pages (from-to)76-83
Number of pages8
JournalCancer Research
Volume58
Issue number1
StatePublished - Jan 1 1998
Externally publishedYes

Fingerprint

Caspase 7
Lovastatin
Prostatic Neoplasms
Apoptosis
Cell Line
Caspases
Mevalonic Acid
Poly(ADP-ribose) Polymerases
Peptide Hydrolases
Caspase 1
Messenger RNA
Caspase Inhibitors
DNA Nucleotidylexotransferase
Agar Gel Electrophoresis
Caspase 3
Culture Media
Oxidoreductases
Cell Death
Up-Regulation
Epithelium

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Marcelli, M., Cunningham, G. R., Haidacher, S. J., Padayatty, S. J., Sturgis, L., Kagan, C., & Denner, L. (1998). Caspase-7 is activated during lovastatin-induced apoptosis of the prostate cancer cell line LNCaP. Cancer Research, 58(1), 76-83.

Caspase-7 is activated during lovastatin-induced apoptosis of the prostate cancer cell line LNCaP. / Marcelli, Marco; Cunningham, Glenn R.; Haidacher, S. Joe; Padayatty, Sebastian J.; Sturgis, Lydia; Kagan, Carolina; Denner, Larry.

In: Cancer Research, Vol. 58, No. 1, 01.01.1998, p. 76-83.

Research output: Contribution to journalArticle

Marcelli, M, Cunningham, GR, Haidacher, SJ, Padayatty, SJ, Sturgis, L, Kagan, C & Denner, L 1998, 'Caspase-7 is activated during lovastatin-induced apoptosis of the prostate cancer cell line LNCaP', Cancer Research, vol. 58, no. 1, pp. 76-83.
Marcelli M, Cunningham GR, Haidacher SJ, Padayatty SJ, Sturgis L, Kagan C et al. Caspase-7 is activated during lovastatin-induced apoptosis of the prostate cancer cell line LNCaP. Cancer Research. 1998 Jan 1;58(1):76-83.
Marcelli, Marco ; Cunningham, Glenn R. ; Haidacher, S. Joe ; Padayatty, Sebastian J. ; Sturgis, Lydia ; Kagan, Carolina ; Denner, Larry. / Caspase-7 is activated during lovastatin-induced apoptosis of the prostate cancer cell line LNCaP. In: Cancer Research. 1998 ; Vol. 58, No. 1. pp. 76-83.
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