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Research ArticleExperimental Studies

Modulation of Anti-apoptosis by Endogenous IAP Expression in MKN45 Human Gastric Cancer Cells

KAZUYA ENDO, SHUNJI KOHNOE, EIJI TSUJITA, AKIHIRO WATANABE, HIDEAKI NAKASHIMA, HIDEO BABA and YOSHIHIKO MAEHARA
Anticancer Research July 2005, 25 (4) 2713-2717;
KAZUYA ENDO
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  • For correspondence: kendo@munakata-med-hp.gr.jp
SHUNJI KOHNOE
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EIJI TSUJITA
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AKIHIRO WATANABE
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HIDEAKI NAKASHIMA
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HIDEO BABA
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YOSHIHIKO MAEHARA
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Abstract

Background: This study was designed to clarify differences in apoptotic signal transduction between gastric cancer cells and leukemia cells. Materials and Methods: In order to study apoptotic signal transduction of gastric cancer cells, MKN45 gastric cancer cells expressing the wild-type p53 gene and U937 myeloid leukemia cells expressing a mutated p53 gene were prepared. Cisplatin (CDDP) was used to induce apoptosis. We compared apoptotic signal transduction downstream to mitochondria between those two lines. Results: In contrast to U937 cells, MKN45 gastric cancer cells revealed delayed response in release of mitochondrial cytochrome c into the cytosol following caspase 3 activation. In signal pathways downstream of caspase 3 cleavage, of the three substrates detected, poly (ADP-ribose) polymerase (PARP) and PKC (protein kinase c) %thou were not activated in MKN45 cells compared with U937 cells, resulting in delayed appearance of DNA ladder formation during CDDP-induced apoptosis. MKN45 constitutively expressed cIAP1, regardless of CDDP treatment, compared with no expression in U937. Drug sensitivity testing showed that MKN45 was more resistant to CDDP than U937 cells. Conclusion: We demonstrated that there is a delayed mitochondrial response and incomplete activation of caspase 3 in MKN45 gastric cancer cells compared with U937 leukemia cells. In addition, there was endogenous cIAP1 expression in MKN45 cells, which may be a factor in the presumed anti-apoptotic system in these human gastric cancer cells.

  • Gastric cancer cell
  • anti-apoptosis
  • IAP
  • inhibitor of apoptosis protein

Footnotes

  • Received December 21, 2004.
  • Accepted April 6, 2005.
  • Copyright© 2005 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved
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Anticancer Research: 25 (4)
Anticancer Research
Vol. 25, Issue 4
1 Jul 2005
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Modulation of Anti-apoptosis by Endogenous IAP Expression in MKN45 Human Gastric Cancer Cells
KAZUYA ENDO, SHUNJI KOHNOE, EIJI TSUJITA, AKIHIRO WATANABE, HIDEAKI NAKASHIMA, HIDEO BABA, YOSHIHIKO MAEHARA
Anticancer Research Jul 2005, 25 (4) 2713-2717;

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Modulation of Anti-apoptosis by Endogenous IAP Expression in MKN45 Human Gastric Cancer Cells
KAZUYA ENDO, SHUNJI KOHNOE, EIJI TSUJITA, AKIHIRO WATANABE, HIDEAKI NAKASHIMA, HIDEO BABA, YOSHIHIKO MAEHARA
Anticancer Research Jul 2005, 25 (4) 2713-2717;
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