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http://dx.doi.org/10.5352/JLS.2007.17.6.778

NADPH oxidase inhibitor diphenyleneiodonium induces p53 expression and cell cycle arrest in several cancer cell lines  

Jo, Hong-Jae (Department of General Surgery, Pusan National University School of Medicine)
Kim, Kang-Mi (Department of Microbiology & Immunology and Medical Research Institute, Pusan National University School of Medicine)
Song, Ju-Dong (Department of Microbiology & Immunology and Medical Research Institute, Pusan National University School of Medicine)
Park, Young-Chul (Department of Microbiology & Immunology and Medical Research Institute, Pusan National University School of Medicine)
Publication Information
Journal of Life Science / v.17, no.6, 2007 , pp. 778-782 More about this Journal
Abstract
The Diphenyleneiodonium (DPI) is widely used as an inhibitor of flavoenzymes, particularly NADPH oxidase. In this study, we investigated the effect of DPI on the cell growth progression of human colon cancer cells HCT-116 (wild-type p53), HT-29 (p53 mutant) and human breast cancer cells MCF-7 (wild-type p53). DPI treatment in cancer cells evoked a dose- and time-dependent growth inhibition, and also induced the cell cycle arrest in C2/M phase. The peak of cell population arrested in C2/M phase was observed at12 hr after treatment of DPI. In addition, DPI significantly induced the expression of p53, which induces proapoptotic genes in response to DNA damage or irreparable cell cycle arrest, at 6 hr in DPI-stimulated cells. However, a catechol apocynin, which inhibits the assembly of NADPH oxidase, did not induce p53 expression. This suggest that p53 expression induced by DPI is not associated with the inhibition of NADPH oxidase. In conclusion, we suggest that DPI induces the expression of wild-type p53 by ROS-in-dependent mechanism in several cancer cells, and upregulated p53 may be involved in regulatory mechanisms for growth inhibition and cell cycle arrest at C2/M phase in DPI-stimulated cells.
Keywords
DPI; growth inhibition; cell cycle arrest; p53; cancer cells;
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