J Cell Biochem. 2008 Aug 15;104(6):2363-73.

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.

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Molecular Mutagenesis and DNA Repair Unit, Department of Epidemiology and Prevention, National Cancer Research Institute (IST), Genova, Italy.

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.

PMID:: 18442053; [PubMed - indexed for MEDLINE]

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