PMID- 19634013 OWN - NLM STAT- MEDLINE DCOM- 20091021 LR - 20090806 IS - 1573-675X (Electronic) IS - 1360-8185 (Linking) VI - 14 IP - 9 DP - 2009 Sep TI - Cell death induced by N-methyl-N-nitrosourea, a model S(N)1 methylating agent, in two lung cancer cell lines of human origin. PG - 1121-33 LID - 10.1007/s10495-009-0379-x [doi] AB - 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 S(N)1 methylating agent, induced cell death through a distinct mechanism in two human NSCLC cell lines studied, A549(p53(wt)) and H157(p53(null)). In A549(p53(wt)), 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(p53(null)), 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 S(N)1 methylating agents is cell type-dependent and must be assessed prior treatment. FAU - Koryllou, Angeliki AU - Koryllou A AD - Institute of Biological Research and Biotechnology, National Hellenic Research Foundation, Athens, Greece. FAU - Patrinou-Georgoula, Meropi AU - Patrinou-Georgoula M FAU - Troungos, Constantinos AU - Troungos C FAU - Pletsa, Vassiliki AU - Pletsa V LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Netherlands TA - Apoptosis JT - Apoptosis : an international journal on programmed cell death JID - 9712129 RN - 0 (Heterogeneous-Nuclear Ribonucleoproteins) RN - 0 (Indoles) RN - 0 (Neoplasm Proteins) RN - 36015-30-2 (Propidium) RN - 47165-04-8 (DAPI) RN - 684-93-5 (Methylnitrosourea) RN - EC 2.4.2.30 (Poly(ADP-ribose) Polymerases) SB - IM MH - Blotting, Western MH - Carcinoma, Non-Small-Cell Lung/*pathology MH - Cell Cycle/drug effects MH - Cell Death/drug effects MH - Cell Line, Tumor MH - Cell Nucleus/drug effects/metabolism MH - Cell Survival/drug effects MH - Heterogeneous-Nuclear Ribonucleoproteins/metabolism MH - Humans MH - Indoles/metabolism MH - Lung Neoplasms/*pathology MH - Methylnitrosourea/*pharmacology MH - Microscopy, Confocal MH - Neoplasm Proteins/metabolism MH - Poly(ADP-ribose) Polymerases/metabolism MH - Propidium/metabolism MH - Staining and Labeling MH - Tumor Stem Cell Assay EDAT- 2009/07/28 09:00 MHDA- 2009/10/22 06:00 CRDT- 2009/07/28 09:00 PHST- 2009/07/28 09:00 [entrez] PHST- 2009/07/28 09:00 [pubmed] PHST- 2009/10/22 06:00 [medline] AID - 10.1007/s10495-009-0379-x [doi] PST - ppublish SO - Apoptosis. 2009 Sep;14(9):1121-33. doi: 10.1007/s10495-009-0379-x.