pgp - publications

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1. Eur J Cancer Prev. 2012 Apr 11. [Epub ahead of print]

Suppression of intestinal polyp development in ApcMin/+ mice through inhibition
of P-glycoprotein using verapamil.

Fujimoto K, Fujii G, Mutoh M, Yasunaga M, Tanaka H, Wada M.

aDivision of Molecular Biology, Nagasaki International University, Nagasaki
bDivision of Cancer Prevention Research, National Cancer Center Research
Institute, Tokyo cDivision of Medical Biochemistry, Kyushu University, Fukuoka,
Japan.

P-glycoprotein (P-gp; encoded by the Mdr1a gene) is known to be associated with
colon tumorigenesis through transcriptional activation and/or epigenetic
modification. We investigated whether inhibition of P-gp function might decrease
intestinal tumorigenesis. We used verapamil as an inhibitor of P-gp function in
Apc mice, which lack a functional Apc gene product. We determined the number of
intestinal polyps and 1-year survival rates after the ingestion of 10, 25, and 50
mg/kg/day verapamil contained in dry pellets. The number of polyps in Mdr1aApc
mice fed with pellets containing verapamil was significantly lower than that in
mice fed with verapamil-free pellets. The 1-year survival rate of verapamil-fed
mice was also improved in a dose-dependent manner. These results were similar to
data from P-gp knockout mice. These results indicated that it might be possible
to use verapamil to inhibit polyp development during the early stage of colon
carcinogenesis. Thus, we propose a novel chemopreventive agent for colorectal
cancer that acts by inhibiting P-gp function.

PMID: 22504657 [PubMed - as supplied by publisher]