Uncoupling Hepatic Oxidative Phosphorylation Reduces Tumor Growth in Two Murine Models of Colon Cancer

2Citations
Citations of this article
20Readers
Mendeley users who have this article in their library.

Abstract

Obesity is associated with colon cancer pathogenesis, but the underlying mechanism is actively debated. Here, we confirm that diet-induced obesity promotes tumor growth in two murine colon cancer models and show that this effect is reversed by an orally administered controlled-release mitochondrial protonophore (CRMP) that acts as a liver-specific uncoupler of oxidative phosphorylation. This agent lowered circulating insulin, and the reduction of tumor growth was abrogated by an insulin infusion raising plasma insulin to the level of high-fat-fed mice. We also demonstrate that hyperinsulinemia increases glucose uptake and oxidation in vivo in tumors and that CRMP reverses these effects. This study provides evidence that perturbations of whole-organism energy balance or hepatic energy metabolism can influence neoplastic growth. Furthermore, the data show that glucose uptake and utilization by cancers in vivo are not necessarily constitutively high but rather may vary according to the hormonal milieu. Wang et al. demonstrate that diet-induced hyperinsulinemia increases colon adenocarcinoma tumor glucose uptake and oxidation in mice. They further demonstrate that reversal of hyperinsulinemia by a liver-specific mitochondrial protonophore is sufficient to reverse the obesity-induced acceleration of tumor growth.

Cite

CITATION STYLE

APA

Wang, Y., Nasiri, A. R., Damsky, W. E., Perry, C. J., Zhang, X. M., Rabin-Court, A., … Perry, R. J. (2018). Uncoupling Hepatic Oxidative Phosphorylation Reduces Tumor Growth in Two Murine Models of Colon Cancer. Cell Reports, 24(1), 47–55. https://doi.org/10.1016/j.celrep.2018.06.008

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free