Inhibition of PARP activity by PJ-34 leads to growth impairment and cell death associated with aberrant mitotic pattern and nucleolar actin accumulation in M14 melanoma cell line

Marta Chevanne, Michele Zampieri, Riccardo Caldini, Angela Rizzo, Fabio Ciccarone, Angela Catizone, Carmen D'Angelo, Tiziana Guastafierro, Anna Biroccio, Anna Reale, Gabriella Zupi, Paola Caiafa

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Abstract

The capability of PARP activity inhibitors to prevent DNA damage recovery suggested the use of these drugs as chemo- and radio-sensitisers for cancer therapy. Our research, carried out on cultured human M14 melanoma cells, was aimed to examine if PJ-34, a potent PARP activity inhibitor of second generation, was per se able to affect the viability of these cancer cells without any DNA damaging agents. Using time-lapse videomicroscopy, we evidenced that 10 μM PJ-34 treatment induced severe mitotic defects leading to dramatic reduction of cell proliferation and to cell death. PJ-34 cytotoxic effect was further confirmed by analysis of cell viability and clonogenic assay. Absence of canonic apoptosis markers allowed us to exclude this kind of cell death. No single and/or double stranded DNA damage was evidenced. Immunofluorescence analysis showed an aberrant mitotic scenario in several cells and subsequent multinucleation suggesting an atypical way for cells to die: the mitotic catastrophe. The detection of aberrant accumulation of polymerised actin inside the nucleolus was noteworthy. Taken toghether, our results demonstrate that, targeting PARP activity by PJ-34, cancer cell survival is affected independently of DNA damage repair. Two findings are remarkable: (a) cisplatin concentration can be reduced by three quarters if it is followed by treatment with 10 μM PJ-34 for 24 h to obtain the same citotoxic effect; (b) effects dependent on PJ-34 treatment are reversible. Our data suggest that, to reduce the harm done to non-tumour cells during chemotherapy with cisplatin, the latter could be coupled with PJ-34 treatment.

Original languageEnglish
Pages (from-to)401-410
Number of pages10
JournalJournal of Cellular Physiology
Volume222
Issue number2
DOIs
Publication statusPublished - Feb 2010

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ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

Cite this

Chevanne, M., Zampieri, M., Caldini, R., Rizzo, A., Ciccarone, F., Catizone, A., D'Angelo, C., Guastafierro, T., Biroccio, A., Reale, A., Zupi, G., & Caiafa, P. (2010). Inhibition of PARP activity by PJ-34 leads to growth impairment and cell death associated with aberrant mitotic pattern and nucleolar actin accumulation in M14 melanoma cell line. Journal of Cellular Physiology, 222(2), 401-410. https://doi.org/10.1002/jcp.21964