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

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 an...

Full description

Saved in:
Bibliographic Details
Published in:Anticancer research 2005-07, Vol.25 (4), p.2713-2717
Main Authors: ENDO, Kazuya, KOHNOE, Shunji, TSUJITA, Eiji, WATANABE, Akihiro, NAKASHIMA, Hideaki, BABA, Hideo, MAEHARA, Yoshihiko
Format: Article
Language:English
Subjects:
Apoptosis - drug effects
Apoptosis - physiology
Biological and medical sciences
Caspase 3
Caspases - metabolism
Cell Line, Tumor
Cisplatin - pharmacology
Cytochromes c - secretion
Drug Screening Assays, Antitumor
Enzyme Activation
Gastroenterology. Liver. Pancreas. Abdomen
Humans
Inhibitor of Apoptosis Proteins
Medical sciences
Mitochondria - secretion
Poly(ADP-ribose) Polymerases - metabolism
Protein Kinase C - metabolism
Protein Kinase C-delta
Proteins - metabolism
Proteins - physiology
Stomach Neoplasms - drug therapy
Stomach Neoplasms - enzymology
Stomach Neoplasms - metabolism
Stomach Neoplasms - pathology
Stomach. Duodenum. Small intestine. Colon. Rectum. Anus
Tumors
U937 Cells
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0250-7005
1791-7530