Discovery of Protein Disulfide Isomerase P5 Inhibitors that Reduce the Secretion of MICA from Cancer Cells. Issue 11 (11th June 2014)

• Record Type: Journal Article
• Authors: Horibe, Tomohisa; Torisawa, Aya; Okuno, Yukiko; Kawakami, Koji
• Is Part Of: Chembiochem. Volume 15:Issue 11(2014)
• Page Start: 1599
• Page End: 1606
• Publication Date: 2014-06-11
• Subjects: Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1002/cbic.201400050
• Languages: English
• ISSNs: 1439-4227

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>In order to regulate the activity of P5, which is a member of the protein disulfide isomerase family, we screened a chemical compound library for P5‐specific inhibitors, and identified two candidate compounds (anacardic acid and NSC74859). Interestingly, anacardic acid inhibited the reductase activity of P5, but did not inhibit the activity of protein disulfide isomerase (PDI), thiol‐disulfide oxidoreductase ERp57, or thioredoxin. NSC74859 inhibited all these enzymes. When we examined the effects of these compounds on the secretion of soluble major histocompatibility complex class‐I‐related gene A (MICA) from cancer cells, anacardic acid was found to decrease secretion. In addition, anacardic acid was found to reduce the concentration of glutathione up‐regulated by the anticancer drug 17‐demethoxygeldanamycin in cancer cells. These results suggest that anacardic acid can both inhibit P5 reductase activity and decrease the secretion of soluble MICA from cancer cells. It might be a novel and potent anticancer treatment by targeting P5 on the surface of cancer cells.</p> </abstract>