{Reference Type}: Journal Article
{Title}: Altered liver metabolism post-wean abolishes efficacy of vitamin D for breast cancer prevention in a mouse model.
{Author}: Bernhardt SM;Ozaki MK;Betts C;Bleyle LA;DeBarber AE;Fornetti J;Liberty AL;Wilde De E;Zhang Y;Xia Z;Schedin P;
{Journal}: bioRxiv
{Volume}: 0
{Issue}: 0
{Year}: 2024 Jun 2
暂无{DOI}: 10.1101/2024.05.28.596304
{Abstract}: Young women have increased risk of vitamin D deficiency, which may increase breast cancer incidence. Here, we assessed the anti-cancer efficacy of vitamin D in mouse models of young-onset breast cancer. In never-pregnant mice, vitamin D supplementation increased serum 25(OH)D and hepatic 1,25(OH)2D3, reduced tumor size, and associated with anti-tumor immunity. These anti-tumor effects were not replicated in a mouse model of postpartum breast cancer, where hepatic metabolism of vitamin D was suppressed post-wean, which resulted in deficient serum 25(OH)D and reduced hepatic 1,25(OH)2D3. Treatment with active 1,25(OH)2D3 induced hypercalcemia exclusively in post-wean mice, highlighting metabolic imbalance post-wean. RNAseq revealed suppressed CYP450 expression postpartum. In sum, we provide evidence that vitamin D anti-tumor activity is mediated through immunomodulatory mechanisms and is ineffective in the post-wean window due to altered hepatic metabolism. These findings have implications for suppressed xenobiotic metabolism in postpartum women beyond vitamin D.