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Discovery of Protein Disulfide Isomerase P5 Inhibitors that Reduce the Secretion of MICA from Cancer Cells
Author(s) -
Horibe Tomohisa,
Torisawa Aya,
Okuno Yukiko,
Kawakami Koji
Publication year - 2014
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201400050
Subject(s) - protein disulfide isomerase , thioredoxin reductase , secretion , biochemistry , chemistry , cancer cell , enzyme , glutathione , isomerase , thioredoxin , reductase , cancer , biology , genetics
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.