Vitamin D Metabolite Profile in Cholecalciferol- or Calcitriol-Supplemented Healthy and Mammary Gland Tumor-Bearing Mice

Abstract

To analyze if the prometastatic activity of calcitriol (active vitamin D3 metabolite), which was previously observed in a 4T1 breast cancer model, is also found in other breast cancers, and to assess the impact of various schemes of vitamin D supply, we used 4T1 and E0771 mouse metastatic and 67NR nonmetastatic cells in this study. BALB/c and C57BL/6 healthy and tumor-bearing mice were exposed to a control (1000 IU), low- (100 IU), and high- (5000 IU) vitamin D3 diets. Additionally, from day 7 of tumor transplantation, the 1000 and 100 IU groups were gavaged with calcitriol (+cal). After 8 weeks of feeding, plasma levels of 25(OH)D3, 24,25(OH)2D3, and 3-epi-25(OH)D3 were significantly lower in calcitriol-treated and vitamin D-deficient groups than in the control, whereas the levels of all metabolites were increased in the 5000 IU group. The ratio of 25(OH)D3:24,25(OH)2D3 was increased in both calcitriol-treated groups, whereas the ratio of 25(OH)D3:3-epi-25(OH)D3 was increased only in the 100 IU group but decreased in the 5000 IU group. In contrast to E0771, 4T1 lung metastasis was accelerated in all vitamin D-supplemented mice, as well as in the deficient group with an increased inflammatory response. 67NR tumor growth was transiently inhibited in the 1000 IU+cal group, but single metastases were observed in the 5000 and 100 IU groups. Based on the results, we conclude that various schemes of vitamin D supply and vitamin D deficiency led to similar metabolite profiles irrespective of the mice strain and tumor burden. However, depending on the type of breast cancer, different effects on tumor growth and metastasis were noticed.

Vitamin D Compounds PRI-2191 and PRI-2205 Enhance Anastrozole Activity in Human Breast Cancer Models

“…After (24 R )-24,25(OH) 2 D 3 treatment, apoptosis induction was observed, which reduced the levels of EMT markers and caused tumor volume reduction in xenograft studies. As shown in the latest studies of Anisiewicz et al, the profile of 25-OH-D 3 : (24 R )-24,25(OH) 2 D 3 in murine plasma did not change significantly between mice strains and tumor burden [ 54 ]. Various regimens of vitamin D supply and vitamin D deficiency led to differences in metabolite profiles independently of the type of breast cancer considered.…”

“…Various regimens of vitamin D supply and vitamin D deficiency led to differences in metabolite profiles independently of the type of breast cancer considered. However, different results were obtained in metastatic and nonmetastatic murine mammary gland cancer models, revealing different effects of vitamin D on tumor growth and metastasis [ 54 ].…”

1,25(OH)2D3 attenuates sleep disturbance in mouse models of Lewis lung cancer, in silico and in vivo

“…It is noteworthy that compared to healthy individuals, cancer patients showed significantly lower blood levels of vitamin D (Penna et al, 2017), and it can perform better and more efficiently if it is targeted at individuals with vitamin D deficiency (Reid et al, 2014). In fact, researchers have tested the circulating vitamin D level of tumorbearing mice, was lower than in control mice (Anisiewicz et al, 2020). (Vieth et al, 1990).…”

Vitamin D, Th17 Lymphocytes, and Breast Cancer

“…On the other hand, Trivedi et al indicated that ablation of VDR (in the absence of ligand) reduced MCF-7 tumor growth in mammary fat pad and in bone [ 141 ]. Furthermore, the authors observed protumoral [ 142 ] or prometastatic activity of calcitriol in prostate [ 143 ] and breast cancer models [ 144 , 145 ].…”