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Induction of Apoptosis by N-methyl-N'-nitro-N-nitrosoguanidine, an Alkylating Agent, in Human Prostate Carcinoma Cells  

Park, Cheol (Department of Biochemistry, Dong-Eui University College of Oriental Medicine, and Research Institute of Oriental Medicine, Department of Biology, Busan National University)
Choi, Byung-Tae (Department of Anatomy, Dong-Eui University College of Oriental Medicine and Research Institute of Oriental Medicine)
Lee, Won-Ho (Department of Biology, Busan National University)
Choi, Yung-Hyun (Department of Biochemistry, Dong-Eui University College of Oriental Medicine, and Research Institute of Oriental Medicine)
Publication Information
Toxicological Research / v.19, no.2, 2003 , pp. 91-98 More about this Journal
Abstract
Alkylating agents form alkylated base adducts in the DNA and cause DNA lesions leading to cell killing. In this study, we investigated the mechanism of apoptosis induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in PC-3 and DU145 human prostate carcinoma cell lines. MNNG treatment resulted in the inhibition of cell proliferation in a concentration-dependent manner to a similar extent in both cell lines. This anti-proliferative effect of PC-3 and DU145 cells by MNNG was associated with morphological changed such as membrane shrinking, cell rounding up and formation of apoptotic bodies. MNNG treatment also induced a proteolytic cleavage of specific target proteins such as poly(ADP-ribose) polymerase (PARP) and $\beta$-catenin proteins in DU145 cells but in PC-3 cells. Furthermore, we observed an increase of proapoptotic protein Bax family expression and a decrease of antiapoptotic protein Bcl-2 family by MNNG treatment in a concentration-dependent manner MNNG also induced a proteolytic activation of caspase-3 and -9, which is believed to play a central role in the apoptotic signaling pathway.
Keywords
MNNG; Apoptosis; Bcl-2/Bax; Caspase;
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