Cell death induced by N-methyl-N-nitrosourea, a model S(N)1 methylating agent, in two lung cancer cell lines of human origin.
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.
Koryllou
Angeliki
A
Institute of Biological Research and Biotechnology, National Hellenic Research Foundation, Athens, Greece.
Patrinou-Georgoula
Meropi
M
Troungos
Constantinos
C
Pletsa
Vassiliki
V
D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000378:metabolism; D006801:Humans; D007211:Indoles / Q000378:metabolism; D008175:Lung Neoplasms / Q000473:pathology*; D008770:Methylnitrosourea / Q000494:pharmacology*; D018613:Microscopy, Confocal; D009363:Neoplasm Proteins / Q000378:metabolism; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011419:Propidium / Q000378:metabolism; D013194:Staining and Labeling; D014410:Tumor Stem Cell Assay
D034441:Heterogeneous-Nuclear Ribonucleoproteins; D007211:Indoles; D009363:Neoplasm Proteins; D011419:Propidium; C007293:DAPI; D008770:Methylnitrosourea; D011065:Poly(ADP-ribose) Polymerases