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KMID : 0379520030190020091
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한국독성학회지
2003 Volume.19 No. 2 p.91 ~ p.98
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Induction of Apoptosis by N-methyl-N’-nitro-N-nitrosoguanidine, an Alkylating Agent, in Human Prostate Carcinoma Cells
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Park Cheol
Choi Byung-Tae
Lee Won-Ho
Choi Yung-Hyun
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Abstract
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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.
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KEYWORD
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MNNG, Apoptosis, Bcl-2/Bax, Caspase
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