Cell death induced by N-methyl-N-nitrosourea, a model SN1 methylating agent, in two lung cancer cell lines of human origin
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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DOI：
10.1007/s10495-009-0379-x
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发表时间：
2009-09-01
期刊：
影响因子：
7.2
通讯作者：
Pletsa, Vassiliki
中科院分区：
文献类型：
--
作者：
Koryllou, Angeliki;Patrinou-Georgoula, Meropi;Pletsa, Vassiliki
肺癌是癌症死亡的主要原因，需要新的治疗方法。甲基化剂是一类广泛使用的抗癌药物，其对人非小细胞肺癌（NSCLC）的作用尚未得到充分研究。N-甲基-N-亚硝基脲（MNU），一种模型S（N）1甲基化剂，通过两种研究的人NSCLC细胞系A549（p53（wt））和H157（p53（null））中的不同机制诱导细胞死亡。在A549（p53（wt））中，MNU诱导G2/M期阻滞，伴随cdc 25 A降解，hnRNP B1诱导，hnRNP C1/C2下调。通过亚G1 DNA含量、聚（ADP-核糖）聚合酶裂解和半胱天冬酶-3，7活化的缺乏增加证实非凋亡性细胞死亡。在H157（p53（null））中，MNU诱导凋亡性细胞死亡，通过DNA含量的细胞荧光测定和凋亡标记物的免疫检测证实，伴随hnRNP B1和C1/C2的过表达。因此，S（N）1甲基化剂诱导的细胞死亡机制是细胞类型依赖性的，必须在治疗前进行评估。
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.