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Cell death induced by N-methyl-N-nitrosourea, a model SN1 methylating agent, in two lung cancer cell lines of human origin

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Abstract

New therapeutic approaches are needed for lung cancer, the leading cause of cancer death. Methylating agents constitute a widely used class of anticancer drugs, the effect of which on human non small cell lung cancer (NSCLC) has not been adequately studied. N-methyl-N-nitrosourea (MNU), a model SN1 methylating agent, induced cell death through a distinct mechanism in two human NSCLC cell lines studied, A549(p53wt) and H157(p53null). In A549(p53wt), MNU induced G2/M arrest, accompanied by cdc25A degradation, hnRNP B1 induction, hnRNP C1/C2 downregulation. Non-apoptotic cell death was confirmed by the lack of increase in the sub-G1 DNA content, Poly (ADP-ribose) polymerase cleavage and caspase-3, -7 activation. In H157(p53null), MNU induced apoptotic cell death, confirmed by cytofluorometry of DNA content and immunodetection of apoptotic markers, accompanied by overexpression of hnRNP B1 and C1/C2. Thus, the mechanism of the cell death induced by SN1 methylating agents is cell type-dependent and must be assessed prior treatment.

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Acknowledgments

We thank Mrs. Irene Kolonti for excellent technical assistance. We also thank Dr. H. Pratsinis (Institute of Biology, Demokritos, Agia Paraskevi, Greece) for useful guidance and discussions throughout the cell cycle analysis experiments and Dr. D. Stellas for his help with the confocal experiments. This work was supported by the research project (PENED), co-financed by EU-European Social Fund (75%) and the Greek Ministry of Development-GSRT (25%).

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  1. Institute of Biological Research and Biotechnology, National Hellenic Research Foundation, Athens, Greece

    Angeliki Koryllou, Meropi Patrinou-Georgoula & Vassiliki Pletsa

  2. Department of Biological Chemistry, School of Medicine, University of Athens, Athens, Greece

    Constantinos Troungos

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  1. Angeliki Koryllou
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  2. Meropi Patrinou-Georgoula
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Koryllou, A., Patrinou-Georgoula, M., Troungos, C. et al. Cell death induced by N-methyl-N-nitrosourea, a model SN1 methylating agent, in two lung cancer cell lines of human origin. Apoptosis 14, 1121–1133 (2009). https://doi.org/10.1007/s10495-009-0379-x

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