Rapid induction of apoptosis in human gastric cancer cell lines by sorbitol.
Most solid tumors, including gastric cancers, respond poorly to non-surgical treatments which are expected to induce an apoptosis-dependent involution. We hypothesize that the apoptotic machinery in solid tumors is either defective or in a suppressed condition. Overcoming the ineffective induction of apoptosis may improve the responsiveness of solid tumors to non-surgical treatments. Recently, sorbitol, a kind of hexose, has been found to be an effective inducer of apoptosis in HEp-2 cells. Therefore, it is of particular interest to examine the effect of sorbitol-treatment on gastric cancer cells. in the present study, we selected 4 gastric cancer cell lines which have been reported to exhibit different abilities in regard to apoptosis induction, and examined the effect of sorbitol-treatment on apoptosis induction. Within 3 hr after sorbitol-treatment, apoptosis was induced comparably in all cell lines examined. Cell death in MKN-1, MKN-28 or MKN-74 proceeded in a biphasic manner, while cell death in KATO-III was monophasic. The cell death partially depended on caspase activity. Treatments with sorbitol in combination with 12-O-tetradecanoylphorbol-13-acetate (TPA) markedly suppressed the apoptotic cell death, suggesting a role of protein kinase-C-dependent process. To our knowledge, this is the most rapid induction of apoptosis in human gastric cancer cells reported to date.
Teramachi
K
K
Department of Biosignaling, Faculty of Medicine, Tottori University, Yonago 683-8503, Japan.
Izawa
M
M
D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D053938:DNA Fragmentation; D006801:Humans; D013012:Sorbitol / Q000494:pharmacology*; D013274:Stomach Neoplasms / Q000378:metabolism / Q000503:physiopathology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000590:Amino Acid Chloromethyl Ketones; D015853:Cysteine Proteinase Inhibitors; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D013012:Sorbitol; D013755:Tetradecanoylphorbol Acetate