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Author Notes:

rmbosti@emory.edu

Conceptualization: Roberd M. Bostick.

Data curation: Yasheen Gao, Caroline Y. Um, Elizabeth L. Barry.

Formal analysis: Yasheen Gao, Caroline Y. Um, Veronika Fedirko.

Funding acquisition: John A. Baron, Roberd M. Bostick.

Investigation: Yasheen Gao, Robin E. Rutherford, March E. Seabrook, Elizabeth L. Barry, John A. Baron, Roberd M. Bostick.

Methodology: Roberd M. Bostick.

Project administration: Roberd M. Bostick.

Resources: Robin E. Rutherford, March E. Seabrook.

Software: Yasheen Gao.

Supervision: Roberd M. Bostick.

Validation: Roberd M. Bostick.

Writing – original draft: Yasheen Gao, Caroline Y. Um, Elizabeth L. Barry, John A. Baron, Roberd M. Bostick.

Writing – review & editing: Yasheen Gao, Caroline Y. Um, Veronika Fedirko, Elizabeth L. Barry, John A. Baron, Roberd M. Bostick.

Subjects:

Research Funding:

This work was supported by the National Cancer Institute- National Institute of Health, Grant Number: R01 CA114456 and R01 CA098286, url: https://www.cancer.gov; the Georgia Cancer Coalition Distinguished Scholar award: http://www.georgiacancer.org/res-distinguished.php; and The Franklin Foundation: https://franklinfdn.org/.

Pfizer Community Healthcare provided the study agents.

The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Keywords:

  • Science & Technology
  • Multidisciplinary Sciences
  • Science & Technology - Other Topics
  • EPITHELIAL-CELL PROLIFERATION
  • NORMAL COLON MUCOSA
  • CANCER
  • PREVENTION
  • MITOCHONDRIA

Effects of supplemental vitamin D and calcium on markers of proliferation, differentiation, and apoptosis in the normal colorectal mucosa of colorectal adenoma patients

Tools:

Journal Title:

PLoS ONE

Volume:

Volume 13, Number 12

Publisher:

, Pages e0208762-e0208762

Type of Work:

Article | Final Publisher PDF

Abstract:

To clarify the roles of vitamin D and calcium as potential chemopreventive agents against colorectal cancer in humans, and to develop “treatable”, pre-neoplastic, phenotypic biomarkers of risk for colorectal neoplasms, we estimated the effects of supplemental vitamin D 3 (1,000 IU/day [25 μg/day]) and calcium (1,200 mg/day), alone and in combination, on biomarkers of proliferation (mib-1), differentiation (p21), and apoptosis (bax [apoptosis-promoting] and bcl-2 [apoptosis-inhibiting]), in the normal-appearing rectal mucosa in a subsample of participants (n = 104) in a larger randomized, double-blind, placebo-controlled clinical trial among colorectal adenoma patients. The biomarkers were measured in rectal biopsies at baseline and after one year of follow up, using automated immunohistochemistry and quantitative image analysis. In the vitamin D plus calcium group relative to control, in the crypt differentiation zone (upper 40% of crypts), mib-1 expression decreased 24% (P = 0.28); p21 expression alone and relative to mib-1 expression increased 29% (P = 0.06) and 73% (P = 0.06), respectively; and bax expression relative to mib-1 expression increased 58% (P = 0.21). The estimated vitamin D alone treatment effects were similar but of lesser magnitudes, and those for calcium alone were mixed. All estimated treatment effects on bcl-2 expression were close to the null. These pilot study results support further investigation of whether 1) vitamin D and calcium promote colorectal epithelial cell differentiation, reduce proliferation, and promote apoptosis in the normal-appearing human colorectal mucosa, 2) vitamin D and calcium act as chemopreventive agents against colorectal neoplasms, and 3) mib-1, p21, and bax are potential “treatable”, pre-neoplastic, biomarkers of risk for colorectal neoplasms.

Copyright information:

© 2018 Gao et al.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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