Dichloroacetate and 5-Fluorouracil

Synergistic Antitumor Effects of Dichloroacetate and 5-Fluorouracil in Colorectal Cancer

Colorectal cancer cells commonly rely on altered energy metabolism to support growth and treatment resistance. Tong and colleagues examined whether dichloroacetate (DCA), a metabolic modulator that shifts cells from glycolysis toward mitochondrial oxidative metabolism, could enhance the effects of 5-fluorouracil (5-FU), a standard chemotherapy used in colorectal cancer.

Using colorectal cancer cell lines and mouse tumor models, the researchers compared treatment with DCA alone, 5-FU alone, and the combination of both agents. They evaluated cancer cell proliferation, apoptosis, tumor growth, and changes in mitochondrial function. This approach allowed them to assess whether modifying cancer metabolism could sensitize tumors to conventional chemotherapy.

The combination of DCA and 5-FU resulted in greater cancer cell death and reduced tumor growth compared with either treatment alone. Mechanistically, DCA appeared to increase mitochondrial activity and promote apoptosis, making cancer cells more vulnerable to 5-FU–induced cytotoxicity. These findings suggest that targeting metabolic pathways may help overcome chemotherapy resistance.

Although this was a preclinical study, it provides important mechanistic insight into how metabolic therapies such as DCA may enhance the effectiveness of established chemotherapies. The results support further investigation in animal and clinical studies to determine whether this strategy could translate into improved outcomes for patients with colorectal cancer.

Reference:

Tong J, Xie G, He J, Li J, Pan F, Liang H. Synergistic antitumor effect of dichloroacetate in combination with 5-fluorouracil in colorectal cancer. J Biomed Biotechnol. 2011;2011:740564. doi:10.1155/2011/740564. PMID: 21403907; PMCID: PMC3043319.