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1alpha,25-(OH)(2)-D(3) and its synthetic analogue decrease tumor load in the Apc(min) Mouse.

Sergio Huerta1, Ronald W Irwin, David Heber

  • 1University of California-Los Angeles Center for Human Nutrition, Los Angeles, CA 90095, USA.

Cancer Research
|February 7, 2002
PubMed
Summary
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A vitamin D analogue significantly reduced intestinal tumor load in mice without causing hypercalcemia, unlike standard vitamin D3. This suggests vitamin D analogues may be effective for colon cancer prevention.

Area of Science:

  • Oncology
  • Endocrinology
  • Gastroenterology

Background:

  • Vitamin D and calcium are implicated in inhibiting colon carcinogenesis.
  • The Apc(min) mouse model is widely used to study intestinal tumor development.

Purpose of the Study:

  • To investigate the chemopreventive effects of 1alpha,25-(OH)(2)-D(3) and a noncalcemic vitamin D analogue in Apc(min) mice.
  • To assess the impact of these compounds on tumor development and serum calcium levels.

Main Methods:

  • Apc(min) mice were treated with 1alpha,25-(OH)(2)-D(3), a vitamin D analogue, or sulindac (positive control).
  • Tumor number and size were assessed, and serum calcium levels were monitored.
  • Reverse transcription-PCR was used to detect vitamin D receptor expression.

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Main Results:

  • The vitamin D analogue significantly decreased total tumor load (36%) and polyp area (70%) without significant hypercalcemia.
  • 1alpha,25-(OH)(2)-D(3) also reduced tumor load (46%) but caused significant hypercalcemia and reduced growth.
  • Sulindac showed significant reductions in polyp number (49%) and area (70%).

Conclusions:

  • A noncalcemic vitamin D analogue effectively reduces intestinal tumor burden in Apc(min) mice.
  • These findings suggest potential utility of vitamin D analogues as chemopreventive agents for high-risk individuals.
  • The study highlights the importance of noncalcemic vitamin D derivatives for cancer prevention to avoid toxicity.