Activation of SAPK and increase in Bak levels during ceramide and indomethacin-induced apoptosis in HT29 cells.
- Author:
Ju Ho KIM
1
;
Sae Ock OH
;
Sung Sook JUN
;
Jin Sup JUNG
;
Jae Suk WOO
;
Yong Keun KIM
;
Sang Ho LEE
Author Information
1. Department of Physiology, College of Medicine Pusan National University, Ami-Dong, Suh-Gu, Pusan South Korea.
- Publication Type:Original Article
- Keywords:
Apoptosis;
Ceramide;
Indomethacin;
HT29 cells
- MeSH:
Apoptosis*;
Cell Line;
Colon;
Colonic Neoplasms;
Epithelial Cells;
HT29 Cells*;
Humans;
Indomethacin;
Protein Kinases
- From:The Korean Journal of Physiology and Pharmacology
1999;3(1):75-82
- CountryRepublic of Korea
- Language:English
-
Abstract:
It has been reported that activation of sphingomyelin pathway and nonsteroidal anti-inflammatory drugs (NSAIDS) inhibit the promotion of colon carcinoma. Ceramide, a metabolite of sphingomyelin, and indomethacin were shown to induce apoptosis in colon carcinoma cells. However, the mechanisms of ceramide- and indomethacin-induced apoptosis in the colon carcinoma cells are not clearly elucidated. Recent studys showed that indomethacin-induced apoptosis in colon cancer cells through the cyclooxygenase-independent pathways, and that may be mediated by generation of ceramide. In this study, we compared effects of ceramide and indomethacin on important modulators of apoptotic processes in HT29 cells, a human colon cancer cell line. Ceramide and indomethacin induced apoptosis dose- and time-dependently. Ceramide and indomethacin increased stress-activated protein kinase (SAPK) activity, and decreased mitogen-activated protein kinase (MAPK) activity. The expression of Bak was increased by the treatment of ceramide and indomethacin. The expression of other Bcl-2 related proteins (Mcl-1, Bcl-XL, Bax) which were known to be expressed in colon epithelial cells was not changed during the ceramide- and indomethacin-induced apoptosis. Our results suggest that ceramide and indomethacin share common mechanisms for induction of apoptosis in HT29 cells.
