Poly (ADP-ribose) polymerase inhibitor increases apoptosis and reduces necrosis induced by a DNA minor groove binding methyl sulfonate ester

L. Tentori, A. Balduzzi, I. Portarena, L. Levati, P. Vernole, B. Gold, E. Bonmassar, G. Graziani

Research output: Contribution to journalArticle

Abstract

The poly(ADP-ribose) polymerase (PARP) is involved in cell recovery from DNA damage, such as methylation of N3-adenine, that activates the base excision repair process. In the present study we demonstrated that MeOSO2(CH2)2-lexitropsin (Me-Lex), a methylating agent that almost exclusively produces N3-methyladenine, induced different modalities of cell death in human leukemic cell lines, depending on the presence of PARP inhibitor. Growth inhibition, provoked by the combination of Me-Lex and PARP inhibitor, was associated with a marked down-regulation of c-myc, increased generation of single strand breaks and apoptosis. When used as single agent, at concentrations that saturated cell repair ability, Me-Lex induced mainly cell death by necrosis. Surprisingly, addition of a PARP inhibitor enhanced apoptosis and reduced the early appearance of necrosis. Telomerase activity was completely suppressed in cells exposed to Me-Lex alone, by 24 h after treatment, whereas it did not change when Me-Lex was combined with PARP inhibitor. Thereafter, inhibition of telomerase was observed with both treatments. The results suggest new insights on different modalities of cell death induced by high levels of N3-methyladenine per se, or by the methylated base in the presence of PARP inhibitor.

Original languageEnglish
Pages (from-to)817-828
Number of pages12
JournalCell Death and Differentiation
Volume8
Issue number8
DOIs
Publication statusPublished - 2001

Fingerprint

Esters
Necrosis
Apoptosis
DNA
Cell Death
Telomerase
Poly(ADP-ribose) Polymerases
Adenine
DNA Repair
Methylation
DNA Damage
Down-Regulation
lexitropsin
Poly(ADP-ribose) Polymerase Inhibitors
Cell Line
Growth
N3-methyladenine

Keywords

  • Apoptosis
  • Drug resistance
  • Methylating agents
  • Necrosis
  • Poly(ADP-ribose) polymerase
  • Telomerase

ASJC Scopus subject areas

  • Cell Biology

Cite this

Poly (ADP-ribose) polymerase inhibitor increases apoptosis and reduces necrosis induced by a DNA minor groove binding methyl sulfonate ester. / Tentori, L.; Balduzzi, A.; Portarena, I.; Levati, L.; Vernole, P.; Gold, B.; Bonmassar, E.; Graziani, G.

In: Cell Death and Differentiation, Vol. 8, No. 8, 2001, p. 817-828.

Research output: Contribution to journalArticle

Tentori, L. ; Balduzzi, A. ; Portarena, I. ; Levati, L. ; Vernole, P. ; Gold, B. ; Bonmassar, E. ; Graziani, G. / Poly (ADP-ribose) polymerase inhibitor increases apoptosis and reduces necrosis induced by a DNA minor groove binding methyl sulfonate ester. In: Cell Death and Differentiation. 2001 ; Vol. 8, No. 8. pp. 817-828.
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