TAILIEUCHUNG - Báo cáo hóa học: " Oxidative stress in NSC-741909-induced apoptosis of cancer cells"

Oxidative stress in NSC-741909-induced apoptosis of cancer cells | Wei et al. Journal of Translational Medicine 2010 8 37 http content 8 1 37 JOURNAL OF TRANSLATIONAL MEDICINE RESEARCH Open Access Oxidative stress in NSC-741909-induced apoptosis of cancer cells Xiaoli Wei21 2 Wei Guo22 Shuhong Wu2 Li Wang2 Peng Huang3 Jinsong Liu4 and Bingliang Fang 2 Abstract Background NSC-741909 is a novel anticancer agent that can effectively suppress the growth of several cell lines derived from lung colon breast ovarian and kidney cancers. We recently showed that NSC-741909-induced antitumor activity is associated with sustained Jun N-terminal kinase JNK activation resulting from suppression of JNK dephosphorylation associated with decreased protein levels of MAPK phosphatase-1. However the mechanisms of NSC-741909-induced antitumor activity remain unclear. Because JNK is frequently activated by oxidative stress in cells we hypothesized that reactive oxygen species ROS may be involved in the suppression of JNK dephosphorylation and the cytotoxicity of NSC-741909. Methods The generation of ROS was measured by using the cell-permeable nonfluorescent compound H2DCF-DA and flow cytometry analysis. Cell viability was determined by sulforhodamine B assay. Western blot analysis immunofluorescent staining and flow cytometry assays were used to determine apoptosis and molecular changes induced by NSC-741909. Results Treatment with NSC-741909 induced robust ROS generation and marked MAPK phosphatase-1 and -7 clustering in NSC-741909-sensitive but not resistant cell lines in a dose- and time-dependent manner. The generation of ROS was detectable as early as 30 min and ROS levels were as high as 6- to 8-fold above basal levels after treatment. Moreover the NSC-741909-induced ROS generation could be blocked by pretreatment with antioxidants such as nordihydroguaiaretic acid aesculetin baicalein and caffeic acid which in turn inhibited the NSC-741909-induced JNK activation and apoptosis. Conclusion Our results demonstrate .

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