Protein disulfide isomerase: a promising target for cancer therapy

Multidrug Resistance-associated Protein-1 (MRP-1)-dependent Glutathione Disulfide (GSSG) Efflux as a Critical Survival Factor for Oxidant-enriched Tumorigenic Endothelial Cells

“…Thiol-disulfide homeostasis is known to be of critical significance in cancer outcomes (70,71). Arresting the glutathione and thioredoxin redox cycles has consistently provided productive returns in killing cancer cells (58,72,73).…”

Protein Disulfide Isomerase: Structure, Mechanism of Oxidative Protein Folding and Multiple Functional Roles

“…The isomerization reaction is driven by energy minimization where the native disulfide bond is energetically favored and thus forms more quickly than the reoxidation of the same nonnative disulfide bond. Once the catalysis reaction is over, PDI is male germ cell thereby it induces cancers or tumors in these organs and cells [67] . The mechanism involved in these diseases states include suppression of apoptosis by PDI which results in the progression of tumor growth and metastasis.…”

“…This further validates that PDI promotes survival and progression of various forms of cancer cells. Hence, inhibitors of PDI may possess therapeutic actions against cancer progression [67] . Recently a series of PACMA (propynoic acid carbamoyl methyl amides) compounds were synthesized that showed potent anticancer activity for human ovarian cancer by inhibiting overexpressed PDI [71] .…”

“…Recent studies have convincingly shown that PDI plays important roles in the physiology as well as pathophysiology of the disease states including diabetes [28] , cardiovascular diseases [66] , cancer [67] neurodegenerative conditions [68] and the entry of pathogens in infectious diseases [69] . However, the precise roles for PDI in each of these diseases have not yet been elucidated.…”

“…Quercetin-3-rutinoside, a flavonol highly abundant in common foods, inhibits PDI and blocks thrombus formation both in vitro and in vivo [31] . It also plays important roles in cancer [32] , neurodegenerative conditions [33] and mediates entry of pathogens in infectious diseases [34] . Keeping the above views in mind, in this review we have discussed PDI structure, catalysis of disulfide bond formation and isomerization and its role as chaperone and in pathophysiology [35] .…”