title: A low carbohydrate, high protein diet combined with celecoxib markedly reduces metastasis.
abstract: We recently demonstrated that both murine and human carcinomas grow significantly slower in mice on low carbohydrate (CHO), high protein diets than on isocaloric Western diets and that a further reduction in tumor growth rates occur when the low CHO diets are combined with the cyclooxygenase-2 inhibitor, celecoxib. Following upon these studies, we asked herein what effect low CHO, high protein diets, with or without celecoxib, might have on tumor metastasis. In the highly metastatic 4T1 mouse mammary tumor model, a 15% CHO, high protein diet supplemented with celecoxib (1 g/kg chow) markedly reduced lung metastases. Moreover, in longer-term studies using male Transgenic Adenocarcinoma of the Mouse Prostate mice, which are predisposed to metastatic prostate cancer, the 15% CHO diet, with and without celecoxib (0.3 g/kg chow), gave the lowest incidence of metastases, but a more moderate 25% CHO diet containing celecoxib led to the best survival. Metabolic studies with 4T1 tumors suggested that the low CHO, high protein diets may be forcing tumors to become dependent on amino acid catabolism for survival/growth. Taken together, our results suggest that a combination of a low CHO, high protein diet with celecoxib substantially reduces metastasis.
authors.affiliation: The Terry Fox Laboratory and.
authors.forename: Victor W
authors.initials: VW
authors.lastname: Ho
authors.affiliation: The Terry Fox Laboratory and The Integrative Oncology Department, BC Cancer Research Centre, 675 West 10th Avenue, Vancouver, British Columbia V5Z 1L3, Canada.
authors.forename: Melisa J
authors.initials: MJ
authors.lastname: Hamilton
authors.affiliation: The Department of Biological Sciences and the Metabolomics Centre, University of Calgary, Calgary, Alberta T2N 1N4, Canada and.
authors.forename: Ngoc-Ha Thi
authors.initials: NH
authors.lastname: Dang
authors.affiliation: The Terry Fox Laboratory and.
authors.forename: Brian E
authors.initials: BE
authors.lastname: Hsu
authors.affiliation: The Vancouver Prostate Centre at Vancouver General Hospital, Vancouver, British Columbia V6H 3Z6, Canada.
authors.forename: Hans H
authors.initials: HH
authors.lastname: Adomat
authors.affiliation: The Vancouver Prostate Centre at Vancouver General Hospital, Vancouver, British Columbia V6H 3Z6, Canada.
authors.forename: Emma S
authors.initials: ES
authors.lastname: Guns
authors.affiliation: The Department of Biological Sciences and the Metabolomics Centre, University of Calgary, Calgary, Alberta T2N 1N4, Canada and.
authors.forename: Aalim
authors.initials: A
authors.lastname: Weljie
authors.affiliation: The Terry Fox Laboratory and.
authors.forename: Ismael
authors.initials: I
authors.lastname: Samudio
authors.affiliation: The Department of Biological Sciences and the Metabolomics Centre, University of Calgary, Calgary, Alberta T2N 1N4, Canada and.
authors.forename: Kevin L
authors.initials: KL
authors.lastname: Bennewith
authors.affiliation: The Terry Fox Laboratory and gkrystal@bccrc.ca.
authors.forename: Gerald
authors.initials: G
authors.lastname: Krystal
mesh_terms: D000818:Animals; D000068579:Celecoxib; D004035:Diet Therapy / Q000379:methods; D050528:Diet, Carbohydrate-Restricted; D004044:Dietary Proteins / Q000494:pharmacology*; D004195:Disease Models, Animal; D008175:Lung Neoplasms / Q000178:diet therapy / Q000188:drug therapy / Q000556:secondary; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009362:Neoplasm Metastasis / Q000188:drug therapy* / Q000628:therapy; D011471:Prostatic Neoplasms / Q000178:diet therapy / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D011720:Pyrazoles / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology*
chemical_list: D004044:Dietary Proteins; D011720:Pyrazoles; D013449:Sulfonamides; D000068579:Celecoxib