PRIMA-1 synergizes with adriamycin to induce cell death in non-small cell lung cancer cells

R. Magrini, D. Russo, L. Ottaggio, G. Fronza, A. Inga, P. Menichini

Research output: Contribution to journalArticle

Abstract

p53-dependent apoptosis is important for the efficacy of cancer treatment, and tumors carrying mutant p53 are often resistant to chemotherapy. Non-small cell lung cancer (NSCLC) cells generally exhibit resistance to apoptosis following treatment with many cytotoxic drugs. The new molecule PRIMA-1 appears to kill human tumor cells by restoring the transcriptional activity to mutated p53. We investigated the induction of apoptosis in response to this drug in three NSCLC cell lines carrying different p53 proteins: A549 (p53wt), LX1 (p53R273H), and SKMes1 (p53R280K). PRIMA-1 alone did not trigger apoptosis but significantly reduced cell viability. However, in combination with adriamycin, PRIMA-1 strengthen the adriamycin-induced apoptosis in A549 and LX1. Interestingly, even in SKMes1 cells, the combined treatment triggered a strong PARP cleavage without DNA fragmentation. Our data suggest that in NSCLC cells, PRIMA-1 may induce cell death through pathways other than apoptosis but may synergize with adriamycin to trigger an apoptotic response.

Original languageEnglish
Pages (from-to)2363-2373
Number of pages11
JournalJournal of Cellular Biochemistry
Volume104
Issue number6
DOIs
Publication statusPublished - Aug 15 2008

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Cell death
Non-Small Cell Lung Carcinoma
Doxorubicin
Cell Death
Cells
Apoptosis
Tumors
Neoplasms
Oncology
Chemotherapy
DNA Fragmentation
Pharmaceutical Preparations
2,2-bis(hydroxymethyl)-1-azabicyclo(2,2,2,)octan-3-one
Cell Survival
Drug Therapy
Cell Line
Molecules
DNA
Therapeutics
Proteins

Keywords

  • Apoptosis
  • Cytotoxicity
  • Non-small cell lung cancer
  • p53
  • PRIMA-1

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

Cite this

PRIMA-1 synergizes with adriamycin to induce cell death in non-small cell lung cancer cells. / Magrini, R.; Russo, D.; Ottaggio, L.; Fronza, G.; Inga, A.; Menichini, P.

In: Journal of Cellular Biochemistry, Vol. 104, No. 6, 15.08.2008, p. 2363-2373.

Research output: Contribution to journalArticle

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AU - Menichini, P.

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