title: 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.
authors.affiliation: Division of Gynecology Oncology, Wayne State University, Detroit, MI.
authors.forename: Zaid
authors.initials: Z
authors.lastname: Al-Wahab
authors.affiliation: Department of Women's Health, Obstetrics and Gynecology, Wayne State University, Detroit, MI.
authors.forename: Calvin
authors.initials: C
authors.lastname: Tebbe
authors.affiliation: Department of Women's Health, Obstetrics and Gynecology, Wayne State University, Detroit, MI.
authors.forename: Jasdeep
authors.initials: J
authors.lastname: Chhina
authors.affiliation: Department of Women's Health, Obstetrics and Gynecology, Wayne State University, Detroit, MI.
authors.forename: Sajad A
authors.initials: SA
authors.lastname: Dar
authors.affiliation: Division of Gynecology Oncology, Wayne State University, Detroit, MI.
authors.forename: Robert T
authors.initials: RT
authors.lastname: Morris
authors.affiliation: Department of Pathology, Karmanos Cancer Institute, Wayne State Univeristy, Detroit, MI.
authors.forename: Rouba
authors.initials: R
authors.lastname: Ali-Fehmi
authors.affiliation: Department of Neurology, Henry Ford Hospital, Detroit, MI.
authors.forename: Shailendra
authors.initials: S
authors.lastname: Giri
authors.affiliation: Department of Women's Health, Obstetrics and Gynecology, Wayne State University, Detroit, MI.
authors.forename: Adnan R
authors.initials: AR
authors.lastname: Munkarah
authors.affiliation: Department of Women's Health, Obstetrics and Gynecology, Wayne State University, Detroit, MI.
authors.forename: Ramandeep
authors.initials: R
authors.lastname: Rattan
mesh_terms: D000818:Animals; D000077216:Carcinoma, Ovarian Epithelial; D018450:Disease Progression; D005260:Female; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009362:Neoplasm Metastasis; D009375:Neoplasms, Glandular and Epithelial / Q000178:diet therapy / Q000378:metabolism* / Q000473:pathology*; D010051:Ovarian Neoplasms / Q000178:diet therapy / Q000378:metabolism* / Q000473:pathology*; D010766:Phosphorylation; D015398:Signal Transduction