Altered liver metabolism post-wean abolishes efficacy of vitamin D for breast cancer prevention in a mouse model.

Autor: Bernhardt SM; Department of Cell, Developmental & Cancer Biology, Oregon Health & Science University, Portland, OR 97239, USA., Ozaki MK; Department of Cell, Developmental & Cancer Biology, Oregon Health & Science University, Portland, OR 97239, USA., Betts C; Department of Cell, Developmental & Cancer Biology, Oregon Health & Science University, Portland, OR 97239, USA., Bleyle LA; Bioanalytical Shared Resource/Pharmacokinetics Core Facility, University Shared Resources, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA., DeBarber AE; Bioanalytical Shared Resource/Pharmacokinetics Core Facility, University Shared Resources, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA., Fornetti J; Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah, 84112, USA., Liberty AL; Division of Complex Family Planning, Department of Obstetrics & Gynecology, Oregon Health & Science University, Portland, OR, 97239, USA., Wilde De E; Department of Cell, Developmental & Cancer Biology, Oregon Health & Science University, Portland, OR 97239, USA., Zhang Y; Computational Biology Program, Oregon Health & Science University, Portland, OR 97201, USA., Xia Z; Computational Biology Program, Oregon Health & Science University, Portland, OR 97201, USA., Schedin P; Department of Cell, Developmental & Cancer Biology, Oregon Health & Science University, Portland, OR 97239, USA.; Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97239, USA.
Jazyk: angličtina
Zdroj: BioRxiv : the preprint server for biology [bioRxiv] 2024 Jun 02. Date of Electronic Publication: 2024 Jun 02.
DOI: 10.1101/2024.05.28.596304
Abstrakt: 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) 2 D 3 , 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) 2 D 3 . Treatment with active 1,25(OH) 2 D 3 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.
Competing Interests: Conflicts of interest: Courtney Betts is an employee of, and holds equity in, Akoya Biosciences, Inc. Andrea DeBarber is a consultant to Leadiant Biosciences, Travere Therapeutics and Mirum Pharma; and serves as a volunteer Medical and Scientific Advisory Board member for the CTX Alliance and the United Leukodystrophy Foundation. The OHSU Foundation and OSHU Departments have received gifts from Travere Therapeutics. These gifts, which have not been made specifically in connection with this research, have been reviewed by the OHSU integrity office. All other authors have no conflicts of interest to disclose.
Databáze: MEDLINE
Externí odkaz: