The Role of Peroxiredoxin V in (-)-Epigallocatechin 3-gallate-Induced Multiple Myeloma Cell Death

Article (PDF Available)inOncology Research Featuring Preclinical and Clinical Cancer Therapeutics 19(8-9):391-8 · September 2011with16 Reads
DOI: 10.3727/096504011X13127606672922 · Source: PubMed
(-)-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.
    • "Dioscin induces esophageal cancer cell apoptosis through downregulation of PRDX1 and 6 [13]. Multiple myeloma cell growth was selectively and significantly reduced by (−)-Epigallocatechin 3-gallate through the downregulation of PRDXs [52] . 4-amino-5- (4-chlorophenyl)-7-(t-butyl)pyrazolo[3, 4-d]pyrimidine (PP2) induces apoptosis and decreases the expression of PRDX3 in human breast cancer MCF-7 cells [22]. "
    [Show abstract] [Hide abstract] ABSTRACT: Snake venom toxin (SVT) from Vipera lebetina turanica contains a mixture of different enzymes and proteins. Peroxiredoxin 6 (PRDX6) is known to be a stimulator of lung cancer cell growth. PRDX6 is a member of peroxidases, and has calcium-independent phospholipase A2 (iPLA2) activities. PRDX6 has an AP-1 binding site in its promoter region of the gene. Since AP-1 is implicated in tumor growth and PRDX6 expression, in the present study, we investigated whether SVT inhibits PRDX6, thereby preventing human lung cancer cell growth (A549 and NCI-H460) through inactivation of AP-1. A docking model study and pull down assay showed that SVT completely fits on the basic leucine zipper (bZIP) region of c-Fos of AP-1. SVT (0-10 μg/ml) inhibited lung cancer cell growth in a concentration dependent manner through induction of apoptotic cell death accompanied by induction of cleaved caspase-3, -8, -9, Bax, p21 and p53, but decreased cIAP and Bcl2 expression via inactivation of AP-1. In an xenograft in vivo model, SVT (0.5 mg/kg and 1 mg/kg) also inhibited tumor growth accompanied with the reduction of PRDX6 expression, but increased expression of proapoptotic proteins. These data indicate that SVT inhibits tumor growth via inhibition of PRDX6 activity through interaction with its transcription factor AP-1.
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    • "Ren [109] demonstrated that (‒)‒epigallocatechin-3-gallate induces reduction in IM9 myelo‐ ma cells and that its activity was dose-and time-dependent on the induction of apoptotic cell death; additionally, this natural metabolite combined with curcumin and lovastatin pos‐ sessed the ability to suppress esophageal cancer-cell growth [154]. In multilla berries, it was found that their high levels of polyphenols, flavonoids, and flavonols and their antioxidants have a strong ability to reduce the viability of colon-cancer HT-29 and SW480 cell lines [33]. "
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  • [Show abstract] [Hide abstract] ABSTRACT: (-)-Epigallocatechin gallate (EGCG), the most abundant component in green tea, has a potent anti-apoptotic activity. The purpose of this study was to investigate the protective effects of EGCG and their molecular mechanisms on high glucose-induced apoptosis of human lens epithelial cells (HLEB-3). HLEB-3 cells were exposed to various concentrations of glucose and EGCG. Cell death was assessed by MTT assay and flow cytometry using annexin V and propidium iodide. The expression of the Bcl-2 family, c-fos, c-myc and p53 was measured by real-time PCR. EGCG decreased the Bcl-2/Bax expression stimulated by a high glucose. Moreover, EGCG suppressed the high glucose-induced expression of c-fos, c-myc and p53. These findings suggest that EGCG protects HLEB-3 cells from high glucose-induced apoptosis by regulating the gene expression of the Bcl-2 family, c-fos, c-myc and p53. Thus, EGCG may have a potential protective effect against diabetic cataract formation.
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