Remodeling of energy metabolism by a ketone body and medium-chain fatty acid suppressed the proliferation of CT26 mouse colon cancer cells

Abstract

Normal and cancerous cells are suggested to have differential utilization of fatty acids and ketone bodies, which could be exploited in cancer therapy. The present study examined the effect of 3-hydroxybutyric acid (3-HBA), which is a ketone body generating acetyl-CoA, and lauric acid (LAA, C12:0), which is a medium-chain saturated fatty acid translocated to mitochondria in a carnitine-independent manner to produce acetyl-CoA, on the energy metabolism of mouse CT26 colon cancer cells. In CT26 cells expressing 3-HBA and LAA transporters, 3-HBA and LAA reduced cell proliferation, mitochondrial volume and lactate production, and increased oxidative stress, particularly in low-glucose conditions. Concurrent treatment with 3-HBA and LAA under glucose starvation had a synergistic effect on cell growth inhibition. In addition, LAA and LAA + 3-HBA promoted an imbalance in the expression of enzymes in the electron transport chain. These findings suggested that treatment with 3-HBA and/or LAA during glucose starvation may reprogram energy metabolism and decrease the proliferation of cancer cells.

Gut Microbes and Microbial Metabolites in Colorectal Cancer Complicated with Different Serum Albumin Levels

“…The recombinant L-methionine gamma-lyase from Brevibacterium aurantiacum can eliminate L-methionine and induce growth arrest and death of CRC cells [43] . Yui, et al reported that 3-hydroxybutyric acid can reprogram energy metabolism during glucose starvation and inhibit the proliferation of CRC cells [44] . The supplementation of glutamic acid can decrease the risk of CRCs [45,46] .…”

Giving combined medium‐chain fatty acids and glucose protects against cancer‐associated skeletal muscle atrophy

“…Notably, LAA suppressed tumor growth. We have previously reported that LAA induces a marked increase in oxidative stress in CT26 cells in vitro, resulting in cell death . CT26 cells were found to have an imbalance in the expression of mitochondrial genes of the electron transport system, and this is thought to be the reason for LAA‐induced oxidative stress through the promotion of oxidative phosphorylation.…”

“…CT26 mouse colon cancer cell line was a kind gift from Professor I.J. Fidler (MD Anderson Cancer Center, Houston, TX, USA) . Human colon cancer cell line HT29 was purchased from Dainihon Pharmacy Co .…”

“…Carbohydrates have been reported to promote cell proliferation in both tumor and skeletal muscle cells in vitro. 24,25 In contrast, MCFA were shown to inhibit the proliferation of tumor cells, 26,27 while there is no evidence of any MFCA-related suppressive effect on skel-…”

Fasting, Fats, and Physics: Combining Ketogenic and Radiation Therapy against Cancer

“…Studies using FDG-PET imaging [25,80] or microdialysis measurements [81] have shown that a KD can downregulate the glycolytic tumor metabolism in some patients. A decrease in tumor lactate production has also been observed in mice kept on a KD [82,83] and in cultured cancer cells treated with ketone bodies [84,85] or fasting-mimicking conditions [86,87]. The decreased tumor lactate concentrations after a few days on a KD in head-and-neck cancer patients measured by Schroeder et al [81] are of particular interest, as tumor lactate concentrations have been directly linked to radioresistance in a variety of xenografted head-and-neck tumors that were irradiated using a clinically relevant schedule of 30 fractions over 6 weeks [88,89].…”