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DRUG:

selenomethionine (SLM)

i
Other names: SLM
Associations
Company:
Holden Comprehensive Cancer Center, The University of Iowa
Drug class:
HIF-2α inhibitor, Autophagy stimulant, HIF-1α inhibitor
Associations
4ms
p38MAPK/HSPB1 is involved in the regulatory effects of selenomethionine on the apoptosis, viability and testosterone secretion of sheep Leydig cells exposed to heat. (PubMed, J Biochem Mol Toxicol)
Furthermore, Se-Met alleviated heat-induced activation of p-p38MAPK/p38MAPK (HE-C vs. HE-S: 1.79-fold, p < 0.05) and p-HSPB1/HSPB1 (HE-C vs. HE-S: 2.72-fold, p < 0.05). In conclusion, p38MAPK/HSPB1 might be involved in Se-Met-mediated alleviation of heat-induced cell apoptosis, cell viability and testosterone secretion impairments in sheep LCs.
Journal • IO biomarker
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BCL2 (B-cell CLL/lymphoma 2) • BAX (BCL2-associated X protein) • HSPB1 (Heat shock 27kDa protein 1)
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selenomethionine (SLM)
4ms
Selenomethionine supplementation mitigates fluoride-induced liver apoptosis and inflammatory reactions by blocking Parkin-mediated mitophagy in mice. (PubMed, Sci Total Environ)
The structure of the mitochondria, mRNA, protein expression levels, and the content of proinflammatory factors in mice from the FParkin-/- and F + SeMetParkin-/- groups closely resembled those in the F + SeMetWT group. Overall, the above results indicated that SeMet could alleviate fluoride-triggered inflammation and apoptosis in mice liver via blocking Parkin-mediated mitophagy.
Preclinical • Journal
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IFNG (Interferon, gamma) • IL6 (Interleukin 6) • TNFA (Tumor Necrosis Factor-Alpha) • SQSTM1 (Sequestosome 1) • IL1B (Interleukin 1, beta)
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selenomethionine (SLM)
5ms
SLM + Axitinib for Clear Cell RCC (clinicaltrials.gov)
P1, N=46, Active, not recruiting, Yousef Zakharia | Phase classification: P1/2 --> P1
Phase classification • Metastases
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Inlyta (axitinib) • selenomethionine (SLM)
6ms
Selenium nanoparticles promotes intestinal development in broilers by inhibiting intestinal inflammation and NLRP3 signaling pathway compared with other selenium sources. (PubMed, Poult Sci)
The control diet was a basal diet added with: 0.2 mg/kg Sodium Selenite (SS-control), 0.2 mg/kg Selenium nano-particles (Nano-Se), 0.2 mg/kg Selenomethionine (SeMet), and 0.2 mg/kg Selenocysteine (Sec) as the treatments...In conclusion, our study demonstrated that Nano-Se and SeMet are better at improving the intestinal health of 21-day-old broilers. Additionally, Nano-Se demonstrated superior antioxidant and anti-inflammatory effects, promoting the development of intestinal goblet cells by modifying the NLRP3 signaling pathway.
Journal
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MYC (V-myc avian myelocytomatosis viral oncogene homolog) • CXCL8 (Chemokine (C-X-C motif) ligand 8) • CLDN1 (Claudin 1) • IL1B (Interleukin 1, beta) • MUC2 (Mucin 2) • NLRP3 (NLR Family Pyrin Domain Containing 3) • TJP1 (Tight Junction Protein 1) • CLDN3 (Claudin 3) • OCLN (Occludin)
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selenomethionine (SLM)
6ms
Supplementation with Combined Additive Improved the Production of Dairy Cows and Their Offspring with Maintenance of Antioxidative Stability. (PubMed, Antioxidants (Basel))
The INC comprised a diverse array of additives, including water-soluble and fat-soluble vitamins, Selenomethionine, and active dry Saccharomyces cerevisiae...Results indicate that supplementation with INC in peripartum dairy cows could be a major strategy to improve immune response, decrease inflammation, maintain antioxidant stress status in transition dairy cows, and have merit in their calves. In conclusion, this study underlines the benefits of INC supplementation during the transition period, as it improved anti-inflammatory capacity, could positively impact antioxidative stress capacity, and eventually enhanced the production performance of dairy cows and the health and growth of calves.
Journal
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IL6 (Interleukin 6) • TNFA (Tumor Necrosis Factor-Alpha)
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selenomethionine (SLM)
6ms
The Influence of N-Acetyl-selenomethionine on Two RONS-Generating Cancer Cell Lines Compared to N-Acetyl-methionine. (PubMed, Cells)
NASeLM could clearly increase caspase-3 activity in both cell types, Jurkat or MTC-SK cells, and thus induce cell death. NALM and NASeLM showed a reduction in cell growth and mitochondrial activity in both cell lines: While NALM and NASeLM showed almost identical measurements on Jurkat cells, NASeLM was much more effective on MTC-SK than the non-selenium-containing carrier, indicating that it has additional anti-chemoprotective effects.
Clinical • Preclinical • Journal
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CASP3 (Caspase 3)
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selenomethionine (SLM)
7ms
Exposure to Selenomethionine and Selenocystine Induces Redox-Mediated ER Stress in Normal Breast Epithelial MCF-10A Cells. (PubMed, Biol Trace Elem Res)
Using a redox-sensitive fluorescent probe targeted to the endoplasmic reticulum (ER), we show that both selenoamino acids shifted the ER redox balance towards an even more oxidizing environment. These results suggest that alteration of the redox state of the ER may disrupt protein folding and cause ER stress-induced apoptosis in MCF-10A cells exposed to selenoamino acids.
Journal
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HSPA5 (Heat Shock Protein Family A (Hsp70) Member 5) • ATF4 (Activating Transcription Factor 4)
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selenomethionine (SLM)
7ms
Optimal Selenium for Bowel Polyps (OSCAR) (clinicaltrials.gov)
P1, N=56, Active, not recruiting, University of Auckland, New Zealand | Trial completion date: Mar 2024 --> Aug 2024 | Trial primary completion date: Dec 2023 --> Jun 2024
Trial completion date • Trial primary completion date
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selenomethionine (SLM)
9ms
Pharmacologic Ascorbate Radiosensitizes Pancreatic Cancer but Radioprotects Normal Tissue: The Role of Oxidative Stress-Induced Lipid Peroxidation. (PubMed, Antioxidants (Basel))
To determine the mechanism, pancreatic cancer cells were treated with selenomethionine or RSL3, an inhibitor of glutathione peroxidase 4 (GPx4). RSL3 treatment inhibited GPx4 activity and increased lipid peroxidation. Differences in oxidative stress may play a role in radioprotecting normal cells while radiosensitizing pancreatic cancer cells when treated with P-AscH-.
Journal
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GPX4 (Glutathione Peroxidase 4)
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RSL3 • selenomethionine (SLM)
10ms
Selenium nanoparticles in aquaculture: Unique advantages in the production of Se-enriched grass carp (Ctenopharyngodon idella). (PubMed, Anim Nutr)
This study evaluated the effects of selenium nanoparticles (SeNP), selenite, and selenomethionine (SeMet) on the growth, antioxidant capacity, selenium content, selenium speciation, and meat quality of grass carp...Furthermore, as an additive, 0.3 mg/kg SeNP significantly improved the flesh quality of grass carp by reducing crude fat and heavy metal content, as well as increasing the levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and the ratio of n-3/n-6 polyunsaturated fatty acid (PUFA). In summary, SeNP is the most suitable additive for producing selenium-enriched fish.
Journal
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BCL2 (B-cell CLL/lymphoma 2) • BAX (BCL2-associated X protein)
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selenomethionine (SLM)
12ms
Selenomethionine Suppress the Progression of Poorly Differentiated Thyroid Cancer via LncRNA NONMMUT014201/miR-6963-5p/Srprb Pathway. (PubMed, Comb Chem High Throughput Screen)
Collectively, SeMet inhibits the growth of PDTC in a dose-dependent manner through LncRNA NONMMUT014201/miR-6963-5p/Srprb signal pathway, thus suggesting that SeMet might be a potential drug for PDTC treatment.
Journal • IO biomarker
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BCL2 (B-cell CLL/lymphoma 2) • MMP2 (Matrix metallopeptidase 2) • CASP3 (Caspase 3) • MMP9 (Matrix metallopeptidase 9) • PCNA (Proliferating cell nuclear antigen) • SRPRB (SRP Receptor Subunit Beta)
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BCL2 expression • SRPRB overexpression • PCNA expression
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selenomethionine (SLM)
12ms
Optimal Selenium for Bowel Polyps (OSCAR) (clinicaltrials.gov)
P1, N=56, Active, not recruiting, University of Auckland, New Zealand
Trial completion date • Trial primary completion date
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selenomethionine (SLM)
1year
Comparing Transcriptomic Responses to Chemicals Across Six Species using the EcoToxChip RNASeq database. (PubMed, Environ Toxicol Chem)
The EcoToxChip project includes RNA-sequencing data from experiments involving model (Japanese quail, fathead minnow, African clawed frog) and ecological (double-crested cormorant, rainbow trout, northern leopard frog) species, at multiple life stages (whole embryo and adult), exposed to eight chemicals of environmental concern known to perturb a wide range of biological systems (ethinyl estradiol, hexabromocyclododecane, lead, selenomethionine, 17β trenbolone, chlorpyrifos, fluoxetine, and benzo[a]pyrene). The most common enriched pathways were metabolic pathways, biosynthesis of cofactors and biosynthesis of secondary metabolites, and chemical carcinogenesis, drug metabolism and metabolism of xenobiotics by Cytochrome P450. The RNA-sequencing database presented here may be used by the research community for multiple purposes, including for example, cross-species investigations, in depth analyses of a particular test compound, and transcriptomic meta-analyses.
Journal
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CYP1A1 (Cytochrome P450 Family 1 Subfamily A Member 1)
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MYC expression
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fluoxetine • selenomethionine (SLM)
1year
Optimal Selenium for Bowel Polyps (OSCAR) (clinicaltrials.gov)
P1, N=56, Active, not recruiting, University of Auckland, New Zealand | Not yet recruiting --> Active, not recruiting
Enrollment closed
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selenomethionine (SLM)
1year
Evaluation of the Neuroprotective Effect of Organic Selenium Compounds: An in Vitro Model of Alzheimer's Disease. (PubMed, Biol Trace Elem Res)
The neuroprotective effect of organic Se compounds, selenomethionine (SeMet) and Ebselen, was evaluated through cell viability tests, acetylcholinesterase and antioxidant enzyme activities, and detection of reactive oxygen species (ROS). Cell differentiation induced by RA and BDNF exposure was effective, showing characteristics of neuronal cells, and pointing to a promising model of AD. Ebselen showed a protective effect, but more studies are needed to identify the mechanism of action.
Preclinical • Journal
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BDNF (Brain Derived Neurotrophic Factor)
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selenomethionine (SLM)
1year
Selenomethionine Attenuated HO-Induced Oxidative Stress and Apoptosis by Nrf2 in Chicken Liver Cells. (PubMed, Antioxidants (Basel))
Moreover, investigations of the mechanism revealed that SM might exert antioxidant effects on HO-induced LMHs by activating the Nrf2 pathway and enhancing the activities of major antioxidant selenoenzymes downstream. These findings provide evidence for the effectiveness of SM on ameliorating HO-induced oxidative impairment and suggest SM has the potential to be used in the prevention or adjuvant treatment of oxidative-related impairment in poultry feeds.
Journal
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BCL2 (B-cell CLL/lymphoma 2) • CASP3 (Caspase 3)
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selenomethionine (SLM)
1year
Selenomethionine suppresses head and neck squamous cell carcinoma progression through TopBP1/ATR and TCAB1 signaling. (PubMed, Histol Histopathol)
Our findings show that SeMet inhibits the proliferation of HNSCC cells and promotes their apoptosis by targeting TopBP1/ATR and TCAB1 signaling. SeMet is a potential method for HNSCC treatment.
Journal
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selenomethionine (SLM)
over1year
Differential Inhibition of Anaplerotic Pyruvate Carboxylation and Glutaminolysis-Fueled Anabolism Underlies Distinct Toxicity of Selenium Agents in Human Lung Cancer. (PubMed, Metabolites)
They largely employed selenomethionine (SeM)-based diets...NSCLC OTC showed similar responses of PyC and/or glutaminolysis to the three agents, which correlated with tissue damages. Altogether, we found differential perturbations in anaplerosis-fueled anabolic pathways to underlie the distinct anti-cancer actions of the three Se agents, which could also explain the failure of SeM-based chemoprevention trials.
Journal
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selenomethionine (SLM)
over1year
Antiproliferative Effect of Inorganic and Organic Selenium Compounds in Breast Cell Lines. (PubMed, Biomedicines)
Therefore, this study aimed to evaluate the effects of exposure to organic (selenomethionine, ebselen, and diphenyl diselenide) and inorganic (sodium selenate and sodium selenite) Se molecules in different breast cell lines. Selenite had a high SI to the BT cell line; however, the SI of ebselen and diphenyl diselenide was low in both tumoral cell lines. In conclusion, the Se compounds had different effects on the breast cell lines, and additional tests are needed to reveal the antiproliferative effects of Se compounds.
Preclinical • Journal
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selenomethionine (SLM)
over1year
Cannabis sativa L. modulates altered metabolic pathways involved in key metabolisms in human breast cancer (MCF-7) cells: A metabolomics study. (PubMed, Heliyon)
MCF-7 cell lines were treated with CSI for 48 h, doxorubicin served as the standard anticancer drug, while untreated MCF-7 cells served as the control...Treatment with CSI caused a 91% depletion of these metabolites, while concomitantly generating selenomethionine, l-cystine, deoxyadenosine triphosphate, cyclic AMP, selenocystathionine, inosine triphosphate, adenosine phosphosulfate, 5'-methylthioadenosine, uric acid, malonic semialdehyde, 2-methylguanosine, ganglioside GD2 and malonic acid...High-performance liquid chromatography (HPLC) analysis of CSI revealed the presence of cannabidiol, rutin, cinnamic acid, and ferulic. These results portray the antiproliferative potentials of CSI as an alternative therapy for the treatment and management of breast cancer as depicted by its modulation of glucose, lipid, amino acid, vitamin, and nucleotide metabolisms, while concomitantly inducing cell death in MCF-7 cells.
Journal • Metabolomic study
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doxorubicin hydrochloride • selenomethionine (SLM)
almost2years
Druggable Biomarkers Altered in Clear Cell Renal Cell Carcinoma: Strategy for the Development of Mechanism-Based Combination Therapy. (PubMed, Int J Mol Sci)
It was demonstrated that HIF, miR, Nrf2, and TGF-ß are targeted by a defined dose and schedule of a specific type of selenium-containing molecules, seleno-L-methionine (SLM) and methylselenocystein (MSC)...Higher selenium doses than those used in clinical prevention trials inhibit multiple targets altered in ccRCC tumors, which could offer the potential for the development of a new and novel therapeutic modality for cancer patients with similar selenium target expression. Better understanding of the underlying mechanisms of selenium modulation of specific targets altered in ccRCC could potentially have a significant impact on the development of a more efficacious and selective mechanism-based combination for the treatment of patients with cancer.
Review • Journal • Combination therapy
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PBRM1 (Polybromo 1) • HIF1A (Hypoxia inducible factor 1, alpha subunit) • ROMO1 (Reactive Oxygen Species Modulator 1)
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HIF1A expression
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selenomethionine (SLM)
2years
Anticancer Properties of Selenium-Enriched Oyster Culinary-Medicinal Mushroom, Pleurotus ostreatus (Agaricomycetes), in Colon Cancer In Vitro. (PubMed, Int J Med Mushrooms)
Notably, the purified selenomethionine (SeMe) showed sufficient inhibition of colon cancer proliferation compared with the inorganic form of selenium (sodium selenite) via blocking the Raf/MEK/ERK signaling pathway...Meanwhile, the SeMe treatment showed a neglected cytotoxic effect in the normal colon epithelial cells. Collectively, these findings indicate that the fruiting bodies of Se-enriched mushrooms revealed anti-colon cancer activity via targeting Raf-1 signaling pathway and increasing the production of IL-6 and IL-10.
Preclinical • Journal
|
IL6 (Interleukin 6) • TNFA (Tumor Necrosis Factor-Alpha) • IL10 (Interleukin 10) • CASP3 (Caspase 3)
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selenomethionine (SLM)
over2years
Effect of Dietary Methylseleninic Acid and Se-Methylselenocysteine on Carcinogen-Induced, Androgen-Promoted Prostate Carcinogenesis in Rats. (PubMed, Nutr Cancer)
Selenomethionine (SeMet) did not prevent prostate cancer in the SELECT trial and in two hormone-driven rat models...Thus, MSeA and MSeC feeding was not preventive in this model. The contrast with the inhibitory effects of MSeA and MSeC in mouse models may be due to differences in carcinogenic mechanisms, selenium dosage, delivery mode, and pharmacokinetics or fundamental rat-mouse differences in selenium metabolism.
Preclinical • Journal
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PTEN (Phosphatase and tensin homolog)
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selenomethionine (SLM)
3years
Potential Role of Seleno-LMethionine (SLM) in Stabilization of Tumor Vasculature and Enhanced Efficacy of Axitinib in Previously Treated Patients with Advanced Clear Cell Renal Cell Carcinoma (ccRCC) (KCRS 2021)
Sarcomatoid ccRCC appears to be less responsive. DECT results suggest that SLM may increase vascularization in tumor tissue while having no impact on normal tissue, leading to increase axi delivery to the tumor.
Clinical
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HIF1A (Hypoxia inducible factor 1, alpha subunit)
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Inlyta (axitinib) • selenomethionine (SLM)
over3years
Selenomethionine alleviates LPS-induced JNK/NLRP3 inflammasome-dependent necroptosis by modulating miR-15a and oxidative stress in chicken lungs. (PubMed, Metallomics)
We also found that LPS treatment not only increased the content of H2O2 and MDA in the lungs but also increased the activities of iNOS and CAT and the content of GSH decreased. SeMet could reduce the oxidative damage and activate NLRP3 inflammasome reaction by stimulating miR-15a/JNK, thus reduced the pulmonary necroptosis induced by LPS.
Journal
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RIPK1 (Receptor Interacting Serine/Threonine Kinase 1) • MAPK8 (Mitogen-activated protein kinase 8) • MIR15A (MicroRNA 15a)
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selenomethionine (SLM)
over3years
Selenomethionine protects hematopoietic stem/progenitor cells against cobalt nanoparticles by stimulating antioxidant actions and DNA repair functions. (PubMed, Aging (Albany NY))
Thus, SeMet enhanced cell cycle arrest and DNA repair post-CoNP exposure. Overall, SeMet protected CD34+ HSCs/HPCs against CoNPs by stimulating antioxidant activity and DNA repair.
Journal
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BRCA1 (Breast cancer 1, early onset) • HIF1A (Hypoxia inducible factor 1, alpha subunit) • CD34 (CD34 molecule)
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selenomethionine (SLM)