Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.4.2.30 (PARP)
 13,611 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Selenocystine (SeC) is a nutritionally available selenoamino acid with selective anticancer effects on a number of human cancer cell lines. The present study shows that SeC inhibited the proliferation of human breast adenocarcinoma MCF-7 cells in a time- and dose-dependent manner, through the induction of cell cycle arrest and apoptotic cell death. SeC-induced S-phase arrest was associated with a marked decrease in the protein expression of cyclins A, D1, and D3 and cyclin-dependent kinases (CDKs) 4 and 6, with concomitant induction of p21waf1/Cip1, p27Kip1, and p53. Exposure of MCF-7 cells to SeC resulted in apoptosis as evidenced by caspase activation, PARP cleavage, and DNA fragmentation. SeC treatment also triggered the activation of JNK, p38 MAPK, ERK, and Akt. Inhibitors of ERK (U0126) and Akt (LY294002), but not JNK (SP600125) and p38 MAPK (SB203580), suppressed SeC-induced S-phase arrest and apoptosis in MCF-7 cells. The findings establish a mechanistic link between the PI3K/Akt pathway, MAPK pathway, and SeC-induced cell cycle arrest and apoptosis in MCF-7 cells.
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PMID:Selenocystine induces S-phase arrest and apoptosis in human breast adenocarcinoma MCF-7 cells by modulating ERK and Akt phosphorylation. 1895 17

Thioredoxin reductase (TrxR) as a selenium (Se)-containing antioxidase plays key role in regulating intracellular redox status. Selenocystine (SeC) a natural available Se-containing amino acid showed novel anticancer potential through triggering oxidative damage-mediated apoptosis. However, whether TrxR-mediated oxidative damage was involved in SeC-induced apoptosis in human glioma cells has not been elucidated yet. Herein, SeC-induced human glioma cell apoptosis was detected in vitro, accompanied by PARP cleavage, caspases activation and DNA fragmentation. Mechanically, SeC caused mitochondrial dysfunction and imbalance of Bcl-2 family expression. SeC treatment also triggered ROS-mediated DNA damage and disturbed the MAPKs and AKT pathways. However, inhibition of ROS overproduction effectively attenuated SeC-induced oxidative damage and apoptosis, and normalized the expression of MAPKs and AKT pathways, indicating the significance of ROS in SeC-induced apoptosis. Importantly, U251 human glioma xenograft growth in nude mice was significantly inhibited in vivo. Further investigation revealed that SeC-induced oxidative damage was achieved by TrxR1-targeted inhibition in vitro and in vivo. Our findings validated the potential of SeC to inhibit human glioma growth by oxidative damage-mediated apoptosis through triggering TrxR1-targeted inhibition.
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PMID:Selenocysteine induces apoptosis in human glioma cells: evidence for TrxR1-targeted inhibition and signaling crosstalk. 2874 99

The rational design and fabrication of nanodelivery systems to encapsulate drugs has been proven to be a promising and effective strategy for cancer therapy. Selenocystine (SeC), a naturally occurring selenoamino acid, has received more and more attention due to its novel pharmacological properties in the treatments of cancers. In this study, we fabricated a cancer-targeted nanodrug delivery system by encapsulating SeC into chitosan (CS) nanoparticles with folate surface decoration (FA-SeC-CSNPs) and evaluated its antiproliferative activities. The nanosystem entered the cells through endocytosis and released SeC in lysosomes under an acidic environment. Compared with SeC-CSNPs and SeC, FA-SeC-CSNPs significantly inhibited the growth of HeLa human cervical cancer cells that overexpressed folate receptors through the induction of apoptosis with the involvement of PARP cleavage and caspase activation. Moreover, FA-SeC-CSNPs also significantly suppressed the migration and invasion of HeLa cells in a dose-dependent manner. Furthermore, the intracellular nanosystem triggered the overproduction of reactive oxygen species (ROS) as early as 25 min after treatment, which activated various downstream signaling pathways such as p53, AKT and MAPKs to induce the cell death. Taken together, this study demonstrates a strategy for rational design of a cancer-targeted nanosystem loaded with selenocompounds to achieve selective cellular uptake and enhanced anticancer efficacy.
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PMID:Rational design and fabrication of a cancer-targeted chitosan nanocarrier to enhance selective cellular uptake and anticancer efficacy of selenocystine. 3226 24