Mechanism of Action of a Novel Analog of Vitamin D, 1 alpha-hydroxy-24-ethyl Cholecalciferol (VD5), in Normal and Transformed Human Breast Epithelial Cells

Abstract

Several epidemiological studies had suggested a correlation between increased breast cancer mortality rates and lower serum levels of vitamin D3. The active form of vitamin D (1,25(OH)2 D3) has now been well recognized as an effective suppressing agent for leukemia, breast, colon, and prostate cancers. However, due to its hypercalcemic activity it is toxic at levels that are necessary for its chemopreventive effects. Therefore, much attention has been paid to developing non-toxic analogs of vitamin D. We have been studying an analog of vitamin D, 1-hydroxy-24-ethyl cholecalciferol (D5), for the past three years. This analog has shown antiproliferative and differentiation inducing effects in carcinogen transformed mouse mammary gland organ culture (MMOC) and breast cancer cells in vitro with little or no calcemic activity in vivo. D5 inhibited preneoplastic lesions and growth of carcinogen treated MMOC, but it had no effect on the growth of normal MMOC. Consequently, we proposed to transform a normal breast epithelial cell line MCFl2F and to study the mechanism of action of D5 on the growth of normal versus transformed cell lines. MCF-12F cells were transformed with DMBA and MNU, and resulting cell lines were designated MCF-l2F(DMBA )and MCF-l2F(MNU), respectively. To study the growth effects of D5 on these cell lines, we performed cell count, cell viability MTT assay and FACS cell cycle analysis.

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Document Details

Document Type
Technical Report
Publication Date
May 01, 2002
Accession Number
ADA406786

Entities

People

  • Erum A. Hussain
  • Rajendra G. Mehta

Organizations

  • University of Illinois at Chicago

Tags

DTIC Thesaurus Topics

  • Breast Cancer
  • Cancer
  • Carcinogens
  • Cell Line
  • Cell Physiological Processes
  • Cells
  • Chemical Synthesis
  • Chemistry
  • Epithelial Cells
  • Health Services
  • Neoplasms
  • Oncology
  • Vitamin D

Fields of Study

  • Medicine

Readers

  • Cellular and Molecular Pathways of Apoptosis.
  • Molecular Biology and Genetics
  • Oncology (Cancer Research).

Technology Areas

  • Biotechnology