AKR1C3 _ DDH3 control peptide
- Known as:
- AKR1C3 _ DDH3 reference short protein sequence
- Catalog number:
- NB100-1940PEP
- Product Quantity:
- 0.1 mg
- Category:
- -
- Supplier:
- ACR
- Gene target:
- AKR1C3 _ DDH3 control peptide
Related genes to: AKR1C3 _ DDH3 control peptide
- Gene:
- AKR1C3 NIH gene
- Name:
- aldo-keto reductase family 1 member C3
- Previous symbol:
- HSD17B5
- Synonyms:
- KIAA0119, DDX, HAKRB, PGFS
- Chromosome:
- 10p15.1
- Locus Type:
- gene with protein product
- Date approved:
- 1998-09-29
- Date modifiied:
- 2016-10-05
Related products to: AKR1C3 _ DDH3 control peptide
Related articles to: AKR1C3 _ DDH3 control peptide
- The vast majority of human malignancies are the result of sustained inflammatory responses. Nowadays, it is well-known that there is a substantial association between inflammation and cancer. The Salvia genus has garnered attention due to its richness of phytochemical profiles with anti-inflammatory and chemopreventive properties. Although the recognized therapeutic potential of Salvia species is recognized, there is considerable variation in their reported chemical composition, and less is known about their compositional differences. In this work, UPLC-HRMS/MS coupled with molecular networking was employed to glean a holistic overview of the chemodiversity of the metabolome of three Salvia species. This was followed by molecular docking of 218 compounds against KEAP1 (PDB: 4IQK) and iNOS (PDB: 1M8D), validated by positive controls. Network pharmacology, Protein-Protein Interaction (PPI), and enrichment analyses identified hub genes (TNF, CASP3, CASP8, PARP1, iNOS, EGFR, PPARG, AKR1C isoforms, and NQO1) linked to inflammatory and antioxidant signaling. Docking analysis predicted that several major compounds may exhibit dual binding affinities, supported by chemoinformatics, ADME, and toxicity predictions. Cirsimaritin was evaluated against AKR1C3 and PARP1 using molecular docking and 100-ns molecular dynamics simulations, representing different stability and interaction profiles between the two targets. The results indicate a dual binding activity, with Cirsimaritin exhibiting primary and stable interaction with AKR1C3 alongside a secondary, dynamic modulatory interaction with PARP1. Mostly bioactive compounds were predominantly found in Salvia multicaulis. The extracts were screened for their in vitro anti-inflammatory and chemoprevention activities. Preliminary experiments confirmed that S. multicaulis acts as an inducer of chemopreventive NAD(P)H: Quinone oxidoreductase 1 (NQO1) protein expression in a murine hepatoma (Hepa1c1c7) chemoprevention model. It also demonstrated the ability to inhibit the lipopolysaccharides (LPS)-induced nitric oxide (NO) production and iNOS protein expression in the RAW264.7 macrophage model. Furthermore, flavonoids and terpenoids were identified to be the major components in this extract, which might be responsible for anti-inflammatory and chemoprevention activities. Our results support the possible application of S. multicaulis in the treatment of human malignancies. - Source: PubMed
Publication date: 2026/06/09
Hamed Ahmed RAli Sherin KAbdel-Halim Sally ABata Shaymaa MHegazi Nesrine MMohamed Tarik AHegazy Mohamed-Elamir F - The diesel exhaust constituent 1-nitropyrene (1-NP) is classified as a probable human carcinogen and other constituents 1,8-dinitropyrene (1,8-DNP) and 3-nitrobenzanthrone (3-NBA) are classified as possible human carcinogens by the International Agency for Research on Cancer. These nitroarenes are activated by nitroreduction via nitroso- and hydroxylamino- intermediates on route to the corresponding amine product(s). Two types of DNA adduct can occur in this sequence. First, the hydroxylamino- intermediate can undergo sulphonation or acetylation giving rise to a strong leaving group so that stable covalent adducts can form. Second, back oxidation of these air sensitive intermediates can give rise to reactive oxygen species and nitrogen species (ROS, RNS) so that oxidatively damaged bases can form. Human aldo-keto reductases AKR1C1, AKR1C2 and AKR1C3 play prominent roles in the nitroreduction of these nitroarenes in human lung cell lines. We now report that when AKR1C1-AKR1C3 are transfected into V79-4 cells we observe a significant increase in HPRT gene mutation. The mutation is dependent on AKR1C enzyme activity since isoform specific inhibitors reduced the number of mutant colonies formed. ROS scavengers reduced the number of mutant colonies formed with 1-NP, 1-8-DNP and 3-NBA in the presence of transfected AKR1C1. Ethyl gallate and the superoxide dismutase mimetic (MnTBAP) reduced the number of mutant colonies formed. Nitric oxide scavengers, 2-(4-carboxyphenyl)-4,5-dihydro-4,4,5,5-tetramethyl-1H-imidazoyl-1-oxy-3-oxide and uric acid, also reduced the number of mutant colonies formed. Our results suggest that both 8-oxo-dG and 8-nitro-dG lesions may contribute to the mutation observed. Since AKR1C1-AKR1C3 are potently induced by NRF2, its activation might increase the mutagenicity of nitroarenes in the context of diesel exhaust exposure. - Source: PubMed
Publication date: 2026/04/17
Su Anthony LMarques Cátia FEl-Bayoumy KaramPenning Trevor M - The potential contribution of foodborne pesticide residues to colorectal cancer (CRC) remains insufficiently understood. In this study, we integrated computational toxicology, network analysis, machine learning, molecular docking, and in vitro validation to investigate possible molecular links between representative foodborne pesticides and CRC. The toxicological properties of ten pesticides were evaluated using ADMETlab 3.0 and ProTox-III. Pesticide-associated target genes were predicted using TargetNet, SuperPred, and the Similarity Ensemble Approach and were intersected with CRC-related genes obtained from GeneCards and OMIM. Functional enrichment analysis showed that the overlapping genes were enriched in xenobiotic response, oxidative stress, and cancer-related pathways. Using random survival forest and least absolute shrinkage and selection operator regression, six hub genes, including PDGFRA, AKR1C3, PDGFRB, CDC42, PIK3CA, and CYP2C9, were identified and used to construct a prognostic model with favorable predictive performance. Among these candidates, AKR1C3 exhibited strong predicted binding affinity with several pesticides, particularly cypermethrin and deltamethrin. Cellular thermal shift assay further supported a direct interaction between cypermethrin and AKR1C3. Cypermethrin reduced cell viability, DNA synthesis, and AKR1C3 protein expression in NCM460 cells. To improve CRC relevance and functional validation, HCT116 colorectal cancer cells were further included. Cypermethrin decreased HCT116 cell viability and AKR1C3 expression, whereas AKR1C3 overexpression partially restored cypermethrin-induced viability reduction and attenuated intracellular ROS accumulation. Together, these findings identify AKR1C3 as a candidate functional target of cypermethrin and suggest that AKR1C3 may be involved, at least in part, in cypermethrin-induced CRC-relevant cellular injury and oxidative stress. This study provides an exploratory framework for identifying exposure-related molecular targets linking foodborne pesticide residues to CRC-associated biological alterations. - Source: PubMed
Publication date: 2026/06/03
Xu HouxiLi XiaoxiaoSun SongxianWang XiaolongLi Yu - The placenta produces a variety of steroid hormones through the catalytic activity of steroidogenic enzymes, including cytochrome P450 (CYP) hydroxylases and hydroxysteroid dehydrogenases (HSD). Large amounts of progesterone produced by the placenta are essential for the maintenance of pregnancy. Although androgens and estrogens are also elevated in maternal circulation during gestation, there are conflicting reports on whether de novo synthesis of these steroids occurs in the human placenta. To address this issue, we performed a comprehensive analysis of steroidogenic gene expression in early and term placenta. While none of the genes examined showed binary expression changes, 17β-HSDs, including HSD17B1 and AKR1C3, were markedly upregulated in the term placenta. CYP19A1 and HSD11B2 genes were also markedly upregulated. In contrast, CYP17A1, CYP21A2, CYP11B1, CYP11B2, and HSD17B3 were almost undetectable. Consistent with these findings, the plasma ratios of active to precursor sex steroids (estradiol/estrone and testosterone/androstenedione) were higher in pregnant than in non-pregnant women, although concentrations of all steroids increased. In contrast, plasma levels and profiles of 11-oxygenated androgens were unchanged. These results indicate that the human placenta does not significantly contribute to circulating levels of either classical or novel classes of androgens. Therefore, this study provides new insights into the tissue of origin and the physiological significance of sex steroids during gestation. - Source: PubMed
Publication date: 2026/05/12
Yokohama YukoWatanabe YugoNakajima Ke-IchiUmezawa AkihiroTakahashi SatoruMori YasuhiroKato YasuhitoKawabe Jun-IchiYazawa Takashi - Breast cancer remains the most prevalent cancer among women, driving the continuous search for novel anticancer agents. In this study, a series of 10-alkoxy steroids containing a 1,4-dien-3-one moiety was synthesized via a one-step dearomatization of the A-ring of estradiol and an estrane derivative with a D-homo lactone moiety. All compounds exhibited favorable in silico ADMET properties, while five derivatives showed significant cytotoxic activity in vitro. The strongest effects against the estrogen-positive breast cancer cell line MCF-7 were observed for two 10β-methoxy, one 10β-butoxy, and two 10β-propargyloxy derivatives. The activity of the 10β-butoxy-17β-hydroxy and 10β-propargyloxy-17β-hydroxy steroids correlates with strong binding affinity toward estrogen receptor α and inhibition of AKR1C3 and AKR1C4 enzymatic activity. Additionally, the propargyloxy derivative showed substrate-like binding to human recombinant aromatase. Molecular docking results are in qualitative agreement with these findings, predicting binding modes similar to known ligands and possible hydrophobic interactions between the C-10 alkoxy groups and the active sites of target proteins, particularly the heme group of aromatase. These results highlight novel estrane derivatives as promising candidates for estrogen-positive breast cancer therapy through combined effects involving AKR1C3 inhibition and interaction with aromatase and estrogen receptor. - Source: PubMed
Kuzminac IvanaBekić SofijaStevanović MilicaScholda JuliaKopp FlorianPetri EdwardĆelić AnđelkaSakač Marija