Dietary energy balance modulates ovarian cancer progression and metastasis

Abstract

A high energy balance, or caloric excess, accounts as a tumor promoting factor, while a negative energy balance via caloric restriction, has been shown to delay cancer progression. The effect of energy balance on ovarian cancer progression was investigated in an isogeneic immunocompetent mouse model of epithelial ovarian cancer kept on a regimen of regular diet, high energy diet (HED) and calorie restricted diet (CRD), prior to inoculating the animals intraperitoneally with the mouse ovarian surface epithelial ID8 cancer cells. Tumor evaluation revealed that mice group on HED displayed the most extensive tumor formation with the highest tumor score at all organ sites (diaphragm, peritoneum, bowel, liver, kidney, spleen), accompanied with increased levels of insulin, leptin, insulin growth factor-1 (IGF-1), monocyte chemoattractant protein-1 (MCP-1), VEGF and interleukin 6 (IL-6). On the other hand, the mice group on CRD exhibited the least tumor burden associated with a significant reduction in levels of insulin, IGF-1, leptin, MCP-1, VEGF and IL-6. Immunohistochemistry analysis of tumors from HED mice showed higher activation of Akt and mTOR with decreased adenosine monophosphate activated kinase (AMPK) and SIRT1 activation, while tumors from the CRD group exhibited the reverse profile. In conclusion, ovarian cancer growth and metastasis occurred more aggressively under HED conditions and was significantly curtailed under CRD. The suggested mechanism involves modulated secretion of growth factors, cytokines and altered regulation of AMPK and SIRT1 that converges on mTOR inhibition. While the role of a high energy state in ovarian cancer has not been confirnmed in the literature, the current findings support investigating the potential impact of diet modulation as adjunct to other anticancer therapies and as possible individualized treatment strategy of epithelial ovarian cancer.

Effects of Dietary Restriction on Cancer Development and Progression

“…Moreover, they showed increased levels of insulin, leptin, IGF-1, VEGF, and proinflammatory factors (IL-6). Instead, the mice group under CR showed a lower tumor burden as well as a great reduction in insulin, IGF-1, leptin, MCP-1, VEGF, and IL-6 levels (Al-Wahab et al 2014). Also, clinical trials demonstrated the effectiveness of the association chemotherapy/DR.…”

“…Al-Wahab et al (2014) published a study showing the effects of energy balance in mouse models subjected to high energy diet or CR conditions. Mice group under high-energy diet showed the most extensive tumor formation accompanied by the highest tumor score at multiple sites.…”

Effects of Dietary Restriction on Cancer Development and Progression

“…Among gynecological tumors, ovarian cancer is one of the most common and the fifth cause of death in the female population (Reid et al 2017). Al-Wahab et al (2014) published a study showing the effects of energy balance in mouse models subjected to high energy diet or CR conditions. Mice group under high-energy diet showed the most extensive tumor formation accompanied by the highest tumor score at multiple sites.…”

Transcriptional Regulation of Chemokine Expression in Ovarian Cancer

“…While hyperglycemia and obesity are thought to be contributing factors to cancer development and progression, caloric restriction has been associated with reduced cancer incidence [ 74 , 75 , 76 , 77 ]. During reduced calorie intake or exercise, the body switches to obtaining energy from fatty acid oxidation, which results in ketone bodies production.…”