title: Impact of CYP24A1 overexpression on growth of colorectal tumour xenografts in mice fed with vitamin D and soy.
abstract: Our previous studies showed that the 1,25-dihydroxyvitamin D (1,25-D3) catabolizing enzyme, 1,25-dihydoxyvitamin D 24 hydroxylase (CYP24A1) was overexpressed in colorectal tumours and its level correlated with increased proliferation. We hypothesised that cells overexpressing CYP24A1 have growth advantage and a diet rich in vitamin D and soy would restore sensitivity to the anti-tumourigenic effects of vitamin D. Soy contains genistein, a natural CYP24A1 inhibitor. To determine causality between CYP24A1 and tumour growth, we established xenografts in male SCID mice with HT29 cells stably overexpressing either GFP-tagged CYP24A1 or GFP. Mice were fed with either high (2500 IU D3/kg) or low vitamin D (100 IU D3/kg) diet in the presence or absence of soy (20% diet). In vitro, cells overexpressing CYP24A1 grew faster than controls. 1,25-D3, the active vitamin D metabolite, reduced cell number only in the presence of the CYP24A1 inhibitor VID400. Regardless of the amount of vitamin D in the diet, xenografts overexpressing CYP24A1 grew faster, were heavier and more aggressive. Soy reduced tumour volume only in the control xenografts, while the tumours overexpressing CYP24A1 were larger in the presence of dietary soy. In conclusion, we demonstrate that CYP24A1 overexpression results in increased aggressiveness and proliferative potential of colorectal tumours. Irrespective of the dietary vitamin D3, dietary soy is able to increase tumour volume when tumours overexpress CYP24A1, suggesting that combination of vitamin D3 and soy could have an anti-tumourigenic effect only if CYP24A1 levels are normal.
authors.affiliation: Department of Pathophysiology and Allergy Research, Medical University of Vienna, Vienna, Austria.
authors.forename: Julia
authors.initials: J
authors.lastname: Höbaus
authors.affiliation: Department of Pathophysiology and Allergy Research, Medical University of Vienna, Vienna, Austria.
authors.forename: Samawansha
authors.initials: S
authors.lastname: Tennakoon
authors.affiliation: Department of Medicine I, Institute of Cancer Research and Comprehensive Cancer Center of the Medical University, Medical University Vienna, Vienna, Austria.|Research Platform 'Translational Cancer Therapy Research', Vienna, Austria.
authors.forename: Petra
authors.initials: P
authors.lastname: Heffeter
authors.affiliation: Department of Pathophysiology and Allergy Research, Medical University of Vienna, Vienna, Austria.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Groeschel
authors.affiliation: Department of Pathophysiology and Allergy Research, Medical University of Vienna, Vienna, Austria.
authors.forename: Abhishek
authors.initials: A
authors.lastname: Aggarwal
authors.affiliation: Department of Pathophysiology and Allergy Research, Medical University of Vienna, Vienna, Austria.
authors.forename: Doris M
authors.initials: DM
authors.lastname: Hummel
authors.affiliation: Department of Pathophysiology and Allergy Research, Medical University of Vienna, Vienna, Austria.|Division of Nephrology and Dialysis, Department of Medicine III, Medical University of Vienna, Vienna, Austria.
authors.forename: Ursula
authors.initials: U
authors.lastname: Thiem
authors.affiliation: Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria.
authors.forename: Rodrig
authors.initials: R
authors.lastname: Marculescu
authors.affiliation: Department of Medicine I, Institute of Cancer Research and Comprehensive Cancer Center of the Medical University, Medical University Vienna, Vienna, Austria.|Research Platform 'Translational Cancer Therapy Research', Vienna, Austria.
authors.forename: Walter
authors.initials: W
authors.lastname: Berger
authors.affiliation: Department of Pathophysiology and Allergy Research, Medical University of Vienna, Vienna, Austria.
authors.forename: Enikö
authors.initials: E
authors.lastname: Kállay
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000473:pathology*; D004195:Disease Models, Animal; D005455:Fluorescent Antibody Technique; D006801:Humans; D008297:Male; D051379:Mice; D016513:Mice, SCID; D020133:Reverse Transcriptase Polymerase Chain Reaction; D045730:Soy Foods; D015854:Up-Regulation; D014807:Vitamin D / Q000494:pharmacology*; D065668:Vitamin D3 24-Hydroxylase / Q000096:biosynthesis*; D023041:Xenograft Model Antitumor Assays
chemical_list: D014807:Vitamin D; D065668:Vitamin D3 24-Hydroxylase
keywords: CYP24A1; colon cancer; soy; vitamin D; xenograft