Growth-inhibitory Effects of the Ketone Body, Monoacetoacetin, on Human Gastric Cancer Cells with Succinyl-CoA: 3-Oxoacid CoA-Transferase (SCOT) Deficiency

Abstract

Background: Monoacetoacetin (MAA) has been used experimentally as a physiological energy source in parenteral nutrition. Succinyl-CoA: 3-oxoacid CoA transferase (SCOT) is a key enzyme in the metabolism of MAA. In this study, the effect of MAA on the growth of human gastric cancer cells was examined in relation to SCOT expression. Materials and Methods: Four gastric cancer cell lines, OCUM-2M, MKN-28, MKN-45 and MKN-74, and two fibroblast cell lines were used in this study. The proliferation of gastric cancer cells was determined by MTT assay, by calculating the number of cancer cells, and by [³H]-thymidine uptake. Cells were cultured in DMEM containing 10% FBS with glucose (4.5 g/L) as the control, or with MAA (4.5 g/L). SCOT mRNA expression was examined by RT-PCR. Results: The growth of OCUM-2M and MKN-28 cells was significantly suppressed in MAA medium compared with glucose medium. In contrast the growth of MKN-74, MKN-45 and normal fibroblasts was not suppressed in MAA medium. SCOT mRNA was expressed in MKN-45, MKN-74 and normal fibroblasts, but not in MKN-28 or OCUM-2M. Conclusion: Parenteral nutrition with MAA may provide preferential energy for patients with some types of gastric cancer with SCOT deficiency.