Butyrate inhibits seeding and growth of colorectal metastases to the liver in mice

Omaida C Velazquez, A. Jabbar, R. P. DeMatteo, J. L. Rombeau

Research output: Contribution to journalArticle

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Abstract

Background. The short-chain fatty acid butyrate inhibits growth of colorectal carcinoma cells in vitro. Mevalonate, a short-chain fatty acid structurally and metabolically related to butyrate, is important in signal transduction and is essential for cell growth. We investigated butyrate's effects on seeding and growth of colorectal tumor cells metastatic to the liver in vivo and hypothesized that butyrate's antiproliferative effects are associated with inhibition of mevalonate-mediated cell growth. Methods. Hepatic metastases were induced by injecting 1 x 105 MC-26 (N-methyl-N-nitrosourea-induced murine colorectal carcinoma) cells into the spleen of BALB/c mice. Mice were treated with a continuous intravenous infusion of butyrate (2 gm/kg/day) for 7 days starting 24 hours before tumor cells were injected. Study variables included liver weight and number of hepatic surface metastases. Proliferation studies on MC-26 cells were performed in vitro to examine the effects of butyrate alone or combined with mevalonate or mevastatin (an inhibitor of mevalonate synthesis). Results. Butyrate reduced seeding and growth of colorectal tumor cells in vivo. Mevalonate diminished butyrate's antiproliferative action in vitro, whereas mevastatin potentiated this effect. Conclusions. These studies (1) show that butyrate inhibits seeding and growth of hepatic colorectal metastases in vivo, (2) associate butyrate's antiproliferative effects with inhibition of mevalonate-mediated cell growth, and (3) indicate that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors may have synergistic antiproliferative effects when combined with butyrate.

Original languageEnglish
Pages (from-to)440-448
Number of pages9
JournalSurgery
Volume120
Issue number2
StatePublished - Sep 11 1996
Externally publishedYes

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Butyrates
Neoplasm Metastasis
Mevalonic Acid
Liver
Growth
Colorectal Neoplasms
Volatile Fatty Acids
Methylnitrosourea
Intravenous Infusions
Signal Transduction
Oxidoreductases
Spleen
Weights and Measures

ASJC Scopus subject areas

  • Surgery

Cite this

Velazquez, O. C., Jabbar, A., DeMatteo, R. P., & Rombeau, J. L. (1996). Butyrate inhibits seeding and growth of colorectal metastases to the liver in mice. Surgery, 120(2), 440-448.

Butyrate inhibits seeding and growth of colorectal metastases to the liver in mice. / Velazquez, Omaida C; Jabbar, A.; DeMatteo, R. P.; Rombeau, J. L.

In: Surgery, Vol. 120, No. 2, 11.09.1996, p. 440-448.

Research output: Contribution to journalArticle

Velazquez, OC, Jabbar, A, DeMatteo, RP & Rombeau, JL 1996, 'Butyrate inhibits seeding and growth of colorectal metastases to the liver in mice', Surgery, vol. 120, no. 2, pp. 440-448.
Velazquez OC, Jabbar A, DeMatteo RP, Rombeau JL. Butyrate inhibits seeding and growth of colorectal metastases to the liver in mice. Surgery. 1996 Sep 11;120(2):440-448.
Velazquez, Omaida C ; Jabbar, A. ; DeMatteo, R. P. ; Rombeau, J. L. / Butyrate inhibits seeding and growth of colorectal metastases to the liver in mice. In: Surgery. 1996 ; Vol. 120, No. 2. pp. 440-448.
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