Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

(-)-Epigallocatechin 3-gallate (EGCG) is a potent antioxidant polyphenol in green tea that acts as an anticancer agent via both direct and indirect pathways. Although the relationship between EGCG's anticancer effects and its antioxidant activity is not fully understood, it is known that EGCG stimulates production of reactive oxygen species (ROS), which induce oxidative stress leading to cell death. In IM9 multiple myeloma cells, EGCG acted in a dose- and time-dependent manner to induce apoptotic cell death. Among the antioxidant enzymes expressed in IM9 cells, levels of peroxiredoxin V (PrdxV) were selectively and significantly reduced by EGCG. Moreover, the ROS scavenger NAC completely inhibited EGCG-induced apoptosis and PrdxV reduction, while overexpression of PrdxV, but not a Prdx(VC48S) mutant, protected IM9 cells from EGCG-induced apoptosis. EGCG-induced reductions in cell viability and PrdxV levels were also observed in primary CD138+ multiple myeloma cells from patients. These results suggest that PrdxV is a key target via which EGCG mediates its anticancer effects.
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PMID:The role of peroxiredoxin V in (-)-epigallocatechin 3-gallate-induced multiple myeloma cell death. 2232 98

B cell malignancies are classified according to the postulated differentiation stage of the originating cell. During differentiation, structural and molecular changes occur to support massive processing of immunoglobulin in the endoplasmic reticulum (ER) of plasma cells at the final stage. When overloaded, the ER generates unfolded proteins and hydrogen peroxide (H2O2), which may cause cell death. Peroxiredoxins (Prxs) I and IV belong to a family of proteins able to catalyze peroxide detoxification. Here, we investigated a potential association of these enzymes with immunoglobulin production in B cell neoplasms. Our results demonstrated that the expression of Prx IV was induced as cells became competent to synthesize immunoglobulin light chains, as observed by immunohistochemistry in tissue sections of B cell neoplasms and also by qPCR and Western blotting analyses in malignant B cell lines. Prx I was frequently highly expressed, indicating additional regulatory processes besides ER activity. Results obtained exclusively with myeloma cells have shown that expression of Prxs I and IV, both at mRNA and protein levels, was associated with light chain secretion quantified by ELISA. We suggest that Prxs I and IV may provide survival advantages for terminally differentiated neoplastic B cells by the elimination of H2O2 and, in the case of Prx IV, by the conversion of this toxic in a functional agent driving oxidative protein folding in the ER. In this sense, multiple myeloma and lymphomas demonstrated to synthesize immunoglobulin chains may benefit from strategic therapies targeting the adaptive pathway to ER stress, including inhibition of Prxs I and IV activity.
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PMID:Expression of peroxiredoxins I and IV in multiple myeloma: association with immunoglobulin accumulation. 2373 84