Retracted: 2-Tellurium-bridged β-cyclodextrin, a thioredoxin reductase inhibitor, sensitizes human breast cancer cells to TRAIL-induced apoptosis through DR5 induction and NF-κB suppression

Abstract

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) exhibits potent antitumor activity via membrane receptors on cancer cells without deleterious side effects for normal tissue. Unfortunately, breast cancer cells, as many other cancer types, develop resistance to TRAIL; therefore, TRAIL sensitizing agents are currently being explored. 2-Tellurium-bridged β-cyclodextrin (2-TeCD) is a synthetic organotellurium compound, with both glutathione peroxidase-like catalytic ability and thioredoxin reductase inhibitor activity. In the present study, we reported that 2-TeCD sensitized TRAIL-resistant human breast cancer cells and xenograft tumors to undergo apoptosis. In vitro, 2-TeCD efficiently sensitized MDA-MB-468 and T47D cells, but not untransformed human mammary epithelial cells, to TRAIL-mediated apoptosis, as evidenced by enhanced caspase activity and poly (adenosine diphosphate-ribose) polymerase cleavage. From a mechanistic standpoint, we showed that 2-TeCD treatment of breast cancer cells significantly upregulated the messenger RNA and protein levels of TRAIL receptor, death receptor (DR) 5, in a transcription factor Sp1-dependent manner. 2-TeCD treatment also suppressed TRAIL-induced nuclear factor-κB (NF-κB) prosurvival pathways by preventing cytosolic IκBα degradation, as well as p65 nuclear translocation. Consequently, the combined administration suppressed anti-apoptotic molecules that are transcriptionally regulated by NF-κB. In vivo, 2-TeCD and TRAIL were well tolerated in mice and their combination significantly inhibited growth of MDA-MB-468 xenografts and promoted apoptosis. Upregulation of DR5 and downregulation of NF-κB by the dual treatment were also observed in tumor tissues. Overall, 2-TeCD sensitizes resistant breast cancer cells to TRAIL-based apoptosis in vitro and in vivo. These findings provide strong evidence for the therapeutic potential of this combination against breast cancers.

Novel Insights into the Synergistic Interaction of a Thioredoxin Reductase Inhibitor and TRAIL: The Activation of the ASK1-ERK-Sp1 Pathway

“…However, we do not provide mechanistic evidence that how this effect achieved and how this effect could be correlated with the TrxR inhibitory activity [28]. In this study, we have examined whether DTCD (a novel synthetic TrxR inhibitor) and TRAIL interact to enhance their cytotoxicity towards ovarian carcinoma cells with the previous results, the present study show that DTCD could also potentiate TRAIL-triggered apoptosis through DR5 up-regulation.…”

Role of miR-149C>T polymorphisms on the risk of hepatocellular carcinoma in a Chinese population

“…Regarding miR-149C>T, it is a proapoptotic miRNA to repress the expression of Akt1 and E2F1. Silencing of Akt1 and E2F1 can induce apoptosis in human tumor cell lines (Lin et al, 2010(Lin et al, , 2011. Previous studies showed that polymorphism in miR-149C>T can change the expression of mature miRNAs or the binding activities to target mRNA, and thus influence cancer risk through various mechanisms (Lin et al, 2010(Lin et al, , 2011.…”

“…Silencing of Akt1 and E2F1 can induce apoptosis in human tumor cell lines (Lin et al, 2010(Lin et al, , 2011. Previous studies showed that polymorphism in miR-149C>T can change the expression of mature miRNAs or the binding activities to target mRNA, and thus influence cancer risk through various mechanisms (Lin et al, 2010(Lin et al, , 2011. Previous studies reported that the association between polymorphism in miR-149C>T and risk of various cancers, such as breast cancer, lung cancer, head and neck cancer, colorectal cancer and HCC, but the results are inconsistent (Hu et al, 2009;Liu et al, 2010;Vinci et al, 2011;Kim et al, 2012;Du et al, 2014).…”

Ultrasensitive ROS-Responsive Coassemblies of Tellurium-Containing Molecules and Phospholipids

“…Organotellurium compounds, which are similar to organoselenium compounds, have been employed as glutathione peroxidase mimics [35][36][37] and described to be promising biomaterials as pharmacological agents for antioxidant and anticarcinogen therapeutics 38,39 . There have been some studies on organotellurium compounds in our group, including coordination responsive telluride-containing polymers 40 and layer by layer films 41 , which can both release cis-platinum in the presence of multi-amine containing molecules (e.g.…”