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Induction of terminal differentiation and apoptosis in human colonic carcinoma cells by brefeldin A, a drug affecting ganglioside biosynthesis
Author(s) -
Nojiri Hisao,
Manya Hiroshi,
Isono Hideo,
Yamana Hideaki,
Nojima Shoshichi
Publication year - 1999
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(99)00709-7
Subject(s) - brefeldin a , ganglioside , forskolin , microbiology and biotechnology , apoptosis , golgi apparatus , cellular differentiation , cell culture , biology , biosynthesis , differentiation therapy , chemistry , biochemistry , cell , gene , genetics , acute promyelocytic leukemia , retinoic acid
An appreciable increase in G M3 with a concomitant decrease in some neolacto‐series gangliosides was observed during differentiation of human colonic carcinoma HCT 116 cells induced by a differentiating agent. When the cells were treated with brefeldin A (BFA), a striking increase in de novo biosynthesis of G M3 and a decrease in biosynthesis of neolacto‐series gangliosides were observed after 6 h. Clear morphological changes to differentiated epithelial cells and an arrest of cells in the G 0 /G 1 phase of the cell cycle were observed after 1 day of treatment. Then the cells were led to apoptosis. This activity was not affected by forskolin, which antagonizes the effects of BFA on protein transport and the Golgi apparatus. These results suggest that the differentiation‐inducing activity of BFA might be due to its modulatory effect on ganglioside biosynthesis, and that a specific change in ganglioside pattern is an essential prerequisite for induction of differentiation, providing a novel target for differentiation therapy of cancer.