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KMID : 1140120090140010060
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Cancer Prevention Research
2009 Volume.14 No. 1 p.60 ~ p.69
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Effects of Deep-sea Water on Apoptosis by N-methyl-N’-nitro-N-nitrosoguanidine in Human Lung Cancer Cells
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Kim Jong-Hwan
Kang Dong-Ho
Choi Yung-Hyun
Hwang Won-Deok
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Abstract
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Deep-sea water (DSW) refers to sea water from a depth of more than 200 meter and is rich in minerals, e.g., Mg, Ca, and K, which have been considered to be associated with prevention and treatment of human diseases. In the present study, we investigated the effect of DSW on apoptotic activity by N-methyl- N’-nitro-N-nitrosoguanidine (MNNG), a monofunctional alkylating agent, in various human cancer cell lines. It was found that MNNG could inhibit the cell growth in a dose-dependent manner, which was associated with dendrite-like morphological change and induction of apoptotic cell death. However, the cells grown in medium containing DSW showed more cytotoxic and apoptotic effects than cells grown in normal medium in A549 lung and AGS gastric cancer cell lines. The increased cytotoxic and apoptotic effects by DSW in A549 cells was associated with the down-regulation of anti-apoptotic Bcl-XL and cIAP-2, and cyclooxygenase-2 expression. Furthermore, the levels of cyclin-dependent kinase inhibitor p21 (WAF1/CIP1) induced by MNNG were enhanced by DSW in a p53-independent manner. Our results suggest a potential role for DSW as anti-apoptotic agents by enhancing apoptosis mediated through the down-regulated expression of Bcl-XL and cIAP-2 and up-regulated expression of p21.
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KEYWORD
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Deep-sea water, Apoptosis, Bcl-XL, cIAP-2, p21
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