Down-regulation of protein kinase C activity by sorbitol rapidly induces apoptosis in human gastric cancer cell lines.
Although apoptosis-dependent involution of malignant tumors is associated with a number of non-surgical treatments including chemotherapy, most solid tumors, including gastric cancers, respond poorly to these therapies. In the hope of overcoming the resistance mechanism against non-surgical therapies, we studied the apoptosis-resistance mechanism in cells of gastric cancers as a model system. During the course of our study on apoptotic machinery in human gastric cancer cell lines, we previously found a rapid and efficient induction of apoptosis by sorbitol. In the present study, we demonstrated that the down-regulation of PKC activity in response to sorbitol is a major factor in the induction of apoptotic cell death in gastric cancer cells.
Izawa
M
M
Department of Biosignaling, Faculty of Medicine, Tottori University, Yonago 683-8503, Japan. 1mizawa@grape.med.tottori-u.ac.jp
Teramachi
K
K
D017209:Apoptosis; D003513:Cycloheximide / Q000494:pharmacology; D015536:Down-Regulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D007700:Kinetics; D008301:Maleimides / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D013012:Sorbitol / Q000494:pharmacology*; D013274:Stomach Neoplasms / Q000201:enzymology / Q000473:pathology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D004791:Enzyme Inhibitors; D007211:Indoles; D008301:Maleimides; D013012:Sorbitol; D003513:Cycloheximide; D011493:Protein Kinase C; C088060:bisindolylmaleimide; D013755:Tetradecanoylphorbol Acetate