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Rapid induction of apoptosis in human gastric cancer cell lines by sorbitol
1Department of Biosignaling, Faculty of Medicine, Tottori University, Yonago 683-8503, Japan.
Abstract:
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.
Insights
Sorbitol rapidly induces apoptosis in gastric cancer cells, offering a potential strategy to enhance treatment responsiveness. This hexose demonstrates a fast-acting mechanism for triggering programmed cell death in various cancer cell lines.
Area of Science:
- Oncology
- Cell Biology
- Biochemistry
Background:
- Solid tumors, including gastric cancers, often resist non-surgical treatments due to defective or suppressed apoptosis.
- Enhancing apoptosis induction could improve the efficacy of treatments for solid tumors.
Purpose of the Study:
- To investigate the effect of sorbitol, a hexose, on inducing apoptosis in human gastric cancer cell lines.
- To determine the kinetics and mechanisms of sorbitol-induced apoptosis in gastric cancer.
Main Methods:
- Four human gastric cancer cell lines with varying apoptosis induction capabilities were treated with sorbitol.
- Apoptosis induction, cell death kinetics, and the role of caspase activity were analyzed.
- The impact of combining sorbitol with 12-O-tetradecanoylphorbol-13-acetate (TPA) was assessed.
Main Results:
- Sorbitol rapidly induced apoptosis comparably across all four gastric cancer cell lines within 3 hours.
- Cell death exhibited biphasic kinetics in MKN-1, MKN-28, and MKN-74, and monophasic kinetics in KATO-III.
- Apoptosis was partially dependent on caspase activity, and protein kinase C (PKC) signaling suppressed sorbitol-induced cell death.
Conclusions:
- Sorbitol is a potent and rapid inducer of apoptosis in human gastric cancer cells.
- This study reports the fastest induction of apoptosis in human gastric cancer cells to date.
- Sorbitol represents a promising agent for overcoming apoptosis resistance in gastric cancer treatment.