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Impact of CYP24A1 overexpression on growth of colorectal tumour xenografts in mice fed with vitamin D and soy
Author(s) -
Höbaus Julia,
Tennakoon Samawansha,
Heffeter Petra,
Groeschel Charlotte,
Aggarwal Abhishek,
Hummel Doris M.,
Thiem Ursula,
Marculescu Rodrig,
Berger Walter,
Kállay Enikö
Publication year - 2015
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.29717
Subject(s) - cyp24a1 , vitamin d and neurology , calcitriol receptor , vitamin , endocrinology , medicine , chemistry , biology
Our previous studies showed that the 1,25‐dihydroxyvitamin D (1,25‐D 3 ) 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 D 3 /kg) or low vitamin D (100 IU D 3 /kg) diet in the presence or absence of soy (20% diet). In vitro, cells overexpressing CYP24A1 grew faster than controls. 1,25‐D 3 , 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 D 3 , dietary soy is able to increase tumour volume when tumours overexpress CYP24A1, suggesting that combination of vitamin D 3 and soy could have an anti‐tumourigenic effect only if CYP24A1 levels are normal.