Protein kinase C isoforms in the chemopreventive effects of a novel vitamin D3 analogue in rat colonic tumorigenesis.

Abstract

BACKGROUND & AIMS:

We recently showed that dietary supplementation with an analogue of 1alpha,25-dihydroxy-vitamin D3, 1alpha,25-dihydroxy-16-ene-23-yne-26,27 F6-vitamin D3 (RO24-5531), reduced the incidence of colonic tumors in rats treated with azoxymethane (AOM). The aim of this study was to determine whether alterations in specific isoforms of protein kinase C (PKC) are involved in this phenomenon.

METHODS:

Protein abundance and subcellular distribution of several PKC isoforms were examined and compared in AOM-induced tumors of rats fed control and RO24-5531-supplemented diets.

RESULTS:

In both AOM-induced colonic adenomas and carcinomas, a significant down-regulation of PKC-alpha, -delta, and -zeta and an up-regulation of PKC-beta11 were found compared with control colonocytes. Dietary RO24-5531 preserved the expression of PKC-zeta and increased the abundance of PKC-epsilon in carcinogen-induced adenomas.

CONCLUSIONS:

Because identical changes in specific isoforms of PKC were found in AOM-induced adenomas and carcinomas, these alterations may be involved in the early stage(s) of colonic malignant transformation. Moreover, the ability of RO24-5531 to block the changes in PKC-zeta induced by AOM, as well as to up-regulate PKC-epsilon, may underlie its ability to prevent adenomas from progressing to carcinomas.

• Authors: R K Wali, M Bissonnette, S Khare, B Aquino, S Niedziela, M Sitrin, T A Brasitus
• Journal: Gastroenterology (Gastroenterology) Vol. 111 Issue 1 Pg. 118-26 (Jul 1996) ISSN: 0016-5085 [Print] United States
• PMID: 8698190 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Anticarcinogenic Agents
• Isoenzymes
• Ro 24-5531
• Protein Kinase C
• Calcitriol
• Azoxymethane

Topics

• Adenocarcinoma (enzymology, pathology, prevention & control)
• Adenoma (enzymology, pathology, prevention & control)
• Animals
• Anticarcinogenic Agents (pharmacology)
• Azoxymethane
• Calcitriol (analogs & derivatives, pharmacology)
• Chemoprevention
• Colon (drug effects, enzymology, pathology)
• Colonic Neoplasms (enzymology, pathology, prevention & control)
• Down-Regulation
• Isoenzymes (metabolism)
• Male
• Protein Kinase C (metabolism)
• Rats
• Rats, Inbred F344
• Up-Regulation