1α,25-(OH)2-D3 and its synthetic analogue decrease tumor load in the Apcmin mouse

Sergio Huerta, Ronald W. Irwin, David Heber, Vay Liang W Go, H. Phillip Koeffler, Milan R. Uskokovic, Diane M. Harris

Research output: Contribution to journalArticle

88 Citations (Scopus)

Abstract

Both calcium and vitamin D are thought to be able to inhibit colon carcinogenesis. To better define the effects of vitamin D, we studied 1α,25-(OH)2-D3 and a noncalcemic synthetic analogue of vitamin D3 (VD3) in the Apcmin mouse. Female Apcmin mice 4-5 weeks old were randomized to four groups: a VD3-treated group (n = 11) were given injections of 0.01 μg of 1α,25-(OH)2-D3 i.p. three times per week; an analogue-treated group (n = 10) received 5 μg of 1α,25-(OH)2-16-ene-19-nor-24-oxo-D3 i.p. three times per week; and a control group (n = 12) received sham injections of PBS. A sulindac-treated group (n = 10) was used as a positive control. Doses of these compounds were chosen based on previous toxicity studies in mice and rats. After 10 weeks of treatment, mice were killed and two observers (S. H., R. W. I.), blinded to treatment, scored polyp number and size. Tumor number was not affected with 1α,25-(OH)2-D3 or vitamin D analogue administration. A significant decrease in total tumor load (sum of all polyp areas) over the entire gastrointestinal tract was seen in the analogue (36% decrease; P < 0.05) and the VD3 groups (46%; P < 0.001). There was a significant decrease in polyp number (49%; P < 0.001) and polyp area (70%; P < 0.001) in the sulindac group. Reverse transcription-PCR of the total RNA derived from intestinal tissue revealed expression of the vitamin D receptor throughout the small intestine and the colon. Serum calcium levels in the analogue group were not elevated at week 4 of treatment and only moderately elevated (22%) by week 8 (P ≤ 0.001). In contrast, serum calcium in the VD3 group was significantly elevated (P ≤ 0.001) at weeks 4 (23%) and 8 (45%). Food intake and growth rate were significantly lower in the VD3 group (26%, P < 0.001, and 27%, P < 0.001, respectively) at week 10. In contrast, food intake and growth rate were similar for the control, sulindac, and analogue groups. Our results indicate that a noncalcemic analogue of vitamin D can significantly decrease intestinal tumor load in Apcmin mice without severe toxic side effects and suggest that these compounds may have utility as chemopreventive agents in groups at high-risk for colon cancer.

Original languageEnglish (US)
Pages (from-to)741-746
Number of pages6
JournalCancer Research
Volume62
Issue number3
StatePublished - Feb 1 2002

Fingerprint

Cholecalciferol
Tumor Burden
Sulindac
Polyps
Vitamin D
Calcium
Colon
Eating
Calcitriol Receptors
Injections
Poisons
Growth
Serum
Colonic Neoplasms
Reverse Transcription
Small Intestine
Gastrointestinal Tract
Carcinogenesis
Therapeutics
RNA

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Huerta, S., Irwin, R. W., Heber, D., Go, V. L. W., Koeffler, H. P., Uskokovic, M. R., & Harris, D. M. (2002). 1α,25-(OH)2-D3 and its synthetic analogue decrease tumor load in the Apcmin mouse. Cancer Research, 62(3), 741-746.

1α,25-(OH)2-D3 and its synthetic analogue decrease tumor load in the Apcmin mouse. / Huerta, Sergio; Irwin, Ronald W.; Heber, David; Go, Vay Liang W; Koeffler, H. Phillip; Uskokovic, Milan R.; Harris, Diane M.

In: Cancer Research, Vol. 62, No. 3, 01.02.2002, p. 741-746.

Research output: Contribution to journalArticle

Huerta, S, Irwin, RW, Heber, D, Go, VLW, Koeffler, HP, Uskokovic, MR & Harris, DM 2002, '1α,25-(OH)2-D3 and its synthetic analogue decrease tumor load in the Apcmin mouse', Cancer Research, vol. 62, no. 3, pp. 741-746.
Huerta S, Irwin RW, Heber D, Go VLW, Koeffler HP, Uskokovic MR et al. 1α,25-(OH)2-D3 and its synthetic analogue decrease tumor load in the Apcmin mouse. Cancer Research. 2002 Feb 1;62(3):741-746.
Huerta, Sergio ; Irwin, Ronald W. ; Heber, David ; Go, Vay Liang W ; Koeffler, H. Phillip ; Uskokovic, Milan R. ; Harris, Diane M. / 1α,25-(OH)2-D3 and its synthetic analogue decrease tumor load in the Apcmin mouse. In: Cancer Research. 2002 ; Vol. 62, No. 3. pp. 741-746.
@article{862a8629a1314d5aa37ccfb61c317a1c,
title = "1α,25-(OH)2-D3 and its synthetic analogue decrease tumor load in the Apcmin mouse",
abstract = "Both calcium and vitamin D are thought to be able to inhibit colon carcinogenesis. To better define the effects of vitamin D, we studied 1α,25-(OH)2-D3 and a noncalcemic synthetic analogue of vitamin D3 (VD3) in the Apcmin mouse. Female Apcmin mice 4-5 weeks old were randomized to four groups: a VD3-treated group (n = 11) were given injections of 0.01 μg of 1α,25-(OH)2-D3 i.p. three times per week; an analogue-treated group (n = 10) received 5 μg of 1α,25-(OH)2-16-ene-19-nor-24-oxo-D3 i.p. three times per week; and a control group (n = 12) received sham injections of PBS. A sulindac-treated group (n = 10) was used as a positive control. Doses of these compounds were chosen based on previous toxicity studies in mice and rats. After 10 weeks of treatment, mice were killed and two observers (S. H., R. W. I.), blinded to treatment, scored polyp number and size. Tumor number was not affected with 1α,25-(OH)2-D3 or vitamin D analogue administration. A significant decrease in total tumor load (sum of all polyp areas) over the entire gastrointestinal tract was seen in the analogue (36{\%} decrease; P < 0.05) and the VD3 groups (46{\%}; P < 0.001). There was a significant decrease in polyp number (49{\%}; P < 0.001) and polyp area (70{\%}; P < 0.001) in the sulindac group. Reverse transcription-PCR of the total RNA derived from intestinal tissue revealed expression of the vitamin D receptor throughout the small intestine and the colon. Serum calcium levels in the analogue group were not elevated at week 4 of treatment and only moderately elevated (22{\%}) by week 8 (P ≤ 0.001). In contrast, serum calcium in the VD3 group was significantly elevated (P ≤ 0.001) at weeks 4 (23{\%}) and 8 (45{\%}). Food intake and growth rate were significantly lower in the VD3 group (26{\%}, P < 0.001, and 27{\%}, P < 0.001, respectively) at week 10. In contrast, food intake and growth rate were similar for the control, sulindac, and analogue groups. Our results indicate that a noncalcemic analogue of vitamin D can significantly decrease intestinal tumor load in Apcmin mice without severe toxic side effects and suggest that these compounds may have utility as chemopreventive agents in groups at high-risk for colon cancer.",
author = "Sergio Huerta and Irwin, {Ronald W.} and David Heber and Go, {Vay Liang W} and Koeffler, {H. Phillip} and Uskokovic, {Milan R.} and Harris, {Diane M.}",
year = "2002",
month = "2",
day = "1",
language = "English (US)",
volume = "62",
pages = "741--746",
journal = "Journal of Cancer Research",
issn = "0099-7013",
publisher = "American Association for Cancer Research Inc.",
number = "3",

}

TY - JOUR

T1 - 1α,25-(OH)2-D3 and its synthetic analogue decrease tumor load in the Apcmin mouse

AU - Huerta, Sergio

AU - Irwin, Ronald W.

AU - Heber, David

AU - Go, Vay Liang W

AU - Koeffler, H. Phillip

AU - Uskokovic, Milan R.

AU - Harris, Diane M.

PY - 2002/2/1

Y1 - 2002/2/1

N2 - Both calcium and vitamin D are thought to be able to inhibit colon carcinogenesis. To better define the effects of vitamin D, we studied 1α,25-(OH)2-D3 and a noncalcemic synthetic analogue of vitamin D3 (VD3) in the Apcmin mouse. Female Apcmin mice 4-5 weeks old were randomized to four groups: a VD3-treated group (n = 11) were given injections of 0.01 μg of 1α,25-(OH)2-D3 i.p. three times per week; an analogue-treated group (n = 10) received 5 μg of 1α,25-(OH)2-16-ene-19-nor-24-oxo-D3 i.p. three times per week; and a control group (n = 12) received sham injections of PBS. A sulindac-treated group (n = 10) was used as a positive control. Doses of these compounds were chosen based on previous toxicity studies in mice and rats. After 10 weeks of treatment, mice were killed and two observers (S. H., R. W. I.), blinded to treatment, scored polyp number and size. Tumor number was not affected with 1α,25-(OH)2-D3 or vitamin D analogue administration. A significant decrease in total tumor load (sum of all polyp areas) over the entire gastrointestinal tract was seen in the analogue (36% decrease; P < 0.05) and the VD3 groups (46%; P < 0.001). There was a significant decrease in polyp number (49%; P < 0.001) and polyp area (70%; P < 0.001) in the sulindac group. Reverse transcription-PCR of the total RNA derived from intestinal tissue revealed expression of the vitamin D receptor throughout the small intestine and the colon. Serum calcium levels in the analogue group were not elevated at week 4 of treatment and only moderately elevated (22%) by week 8 (P ≤ 0.001). In contrast, serum calcium in the VD3 group was significantly elevated (P ≤ 0.001) at weeks 4 (23%) and 8 (45%). Food intake and growth rate were significantly lower in the VD3 group (26%, P < 0.001, and 27%, P < 0.001, respectively) at week 10. In contrast, food intake and growth rate were similar for the control, sulindac, and analogue groups. Our results indicate that a noncalcemic analogue of vitamin D can significantly decrease intestinal tumor load in Apcmin mice without severe toxic side effects and suggest that these compounds may have utility as chemopreventive agents in groups at high-risk for colon cancer.

AB - Both calcium and vitamin D are thought to be able to inhibit colon carcinogenesis. To better define the effects of vitamin D, we studied 1α,25-(OH)2-D3 and a noncalcemic synthetic analogue of vitamin D3 (VD3) in the Apcmin mouse. Female Apcmin mice 4-5 weeks old were randomized to four groups: a VD3-treated group (n = 11) were given injections of 0.01 μg of 1α,25-(OH)2-D3 i.p. three times per week; an analogue-treated group (n = 10) received 5 μg of 1α,25-(OH)2-16-ene-19-nor-24-oxo-D3 i.p. three times per week; and a control group (n = 12) received sham injections of PBS. A sulindac-treated group (n = 10) was used as a positive control. Doses of these compounds were chosen based on previous toxicity studies in mice and rats. After 10 weeks of treatment, mice were killed and two observers (S. H., R. W. I.), blinded to treatment, scored polyp number and size. Tumor number was not affected with 1α,25-(OH)2-D3 or vitamin D analogue administration. A significant decrease in total tumor load (sum of all polyp areas) over the entire gastrointestinal tract was seen in the analogue (36% decrease; P < 0.05) and the VD3 groups (46%; P < 0.001). There was a significant decrease in polyp number (49%; P < 0.001) and polyp area (70%; P < 0.001) in the sulindac group. Reverse transcription-PCR of the total RNA derived from intestinal tissue revealed expression of the vitamin D receptor throughout the small intestine and the colon. Serum calcium levels in the analogue group were not elevated at week 4 of treatment and only moderately elevated (22%) by week 8 (P ≤ 0.001). In contrast, serum calcium in the VD3 group was significantly elevated (P ≤ 0.001) at weeks 4 (23%) and 8 (45%). Food intake and growth rate were significantly lower in the VD3 group (26%, P < 0.001, and 27%, P < 0.001, respectively) at week 10. In contrast, food intake and growth rate were similar for the control, sulindac, and analogue groups. Our results indicate that a noncalcemic analogue of vitamin D can significantly decrease intestinal tumor load in Apcmin mice without severe toxic side effects and suggest that these compounds may have utility as chemopreventive agents in groups at high-risk for colon cancer.

UR - http://www.scopus.com/inward/record.url?scp=0036462480&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036462480&partnerID=8YFLogxK

M3 - Article

C2 - 11830528

AN - SCOPUS:0036462480

VL - 62

SP - 741

EP - 746

JO - Journal of Cancer Research

JF - Journal of Cancer Research

SN - 0099-7013

IS - 3

ER -