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KMID : 0811719990030010075
Korean Journal of Physiology & Pharmacology
1999 Volume.3 No. 1 p.75 ~ p.82
Activation of SAPK and Increase in Bak Levels during Ceramide and Indomethacin-Induced Apoptosis in HT29 Cells
Ju Ho Kim
Sae Ock Oh/Sung Sook Jun/Jin Sup Jung/Jae Suk Woo/Yong Keun Kim/Sang Ho Lee
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.
KEYWORD
Apoptosis, Ceramide, Indomethacin, HT29 cells,
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