Steroid sulfatase suppresses keratinization by inducing proteasomal degradation of E-cadherin via Hakai regulation.

X-linked ichthyosis (XLI) is a genetic disorder characterized by a steroid sulfatase (STS) deficiency inducing excessive cholesterol sulfate accumulation and keratinization. Our study utilizes STS knockout mice to reproduce the hyperkeratinization typical of XLI, providing a valuable model for investigating the underlying mechanisms. From the experiment of STS-deficient keratinocytes using the CRISPR/Cas9 system, we observed upregulation of E-cadherin, which is associated with keratinocyte differentiation and stratification.

Upregulation of YPEL3 expression and induction of human breast cancer cell death by microRNAs.

Unlabelled: MicroRNAs (miRNAs), molecules comprising 18-22 nucleotides, regulate expression of genes post-transcriptionally at the 3' untranslated region of target mRNAs. However, the biological roles and mechanisms of action of miRNAs in breast cancer remain unelucidated. Thus, in this study, we aimed to investigate the functions and possible mechanisms of action of miRNAs in breast cancer to suppress carcinogenesis.

Correction: Upregulation of YPEL3 expression and induction of human breast cancer cell death by microRNAs.

[This corrects the article DOI: 10.1007/s43188-024-00251-2.].

Unraveling the molecular mechanisms of cell migration impairment and apoptosis associated with steroid sulfatase deficiency: Implications for X-linked ichthyosis.

Steroid sulfatase (STS) deficiency is responsible for X-linked ichthyosis (XLI), a genetic disorder characterized by rough and dry skin caused by excessive keratinization. The impaired keratinization process leads to reduced cell mobility and increased apoptosis, which can cause an excessive buildup of the stratum corneum. In this study, we investigated the mechanisms underlying XLI and found that STS deficiency reduces cell mobility and increases apoptosis in human keratinocyte HaCaT cells.

YPEL3 expression induces cellular senescence via the Hippo signaling pathway in human breast cancer cells.

The Hippo pathway is a signaling pathway that controls organ size in animals by regulating cell proliferation and apoptosis. Yes-associated protein 1 (YAP1), an oncogene associated with the development and progression of breast cancer, is downregulated by the Hippo pathway and is associated with the development and progression of breast cancer. Yippee-like 3 (YPEL3) is a target gene of the tumor suppressor protein p53, and its activation has been shown to inhibit cell growth, induce cellular senescence, and suppress tumor cell metastasis.

Enhancing the invasive traits of breast cancers by CYP1B1 via regulation of p53 to promote uPAR expression.

Human cytochrome P450 1B1 (CYP1B1) catalyzes estrogen metabolism to produce metabolites that promote the progression of breast cancer. Since the invasive properties of cancer cells cause cancer relapse, which dramatically reduces patient survival, we investigated the new pro-invasive mechanism involving CYP1B1 in breast cancer. Exploring clinical data from invasive breast cancer patients revealed that CYP1B1 exhibits a potential correlation with urokinase-type plasminogen activator receptor (uPAR).

Induction of synergistic apoptosis by tetramethoxystilbene and nutlin-3a in human cervical cancer cells.

2,4,3',5'-Tetramethoxystilbene (TMS) is a selective inhibitor of cytochrome P450 1B1 to block the conversion from estradiol to 4-OH-estradiol. Several studies suggested that TMS may act as a potent anti-cancer agent for hormone-related cancer including cervical cancer. Nutlin-3a is a cis-imidazoline analog that interferes with the interaction between mouse double minute 2 homolog (MDM2) and the tumor suppressor p53.

Functional Characterization of CYP6A8 Fatty Acid Hydroxylase.

Genomic analysis indicated that the genome of contains more than 80 cytochrome P450 genes. To date, the enzymatic activity of these P450s has not been extensively studied. Here, the biochemical properties of CYP6A8 were characterized.

Anticancer activity and metabolic profile alterations by ortho-topolin riboside in in vitro and in vivo models of non-small cell lung cancer.

Lung cancer has the highest incidence and mortality rates among all types of cancer worldwide, and 80%-85% of patients with lung cancer are diagnosed with non-small cell lung cancer (NSCLC), which has 5-year survival rate of only 5% at advanced stages. Development of new therapeutic agents and strategies is required to enhance the treatment efficiency in patients with NSCLC. Metabolic alterations and anticancer effects of plant hormones and their derivatives have not been investigated in NSCLC in vitro and in vivo.

Steroid sulfatase deficiency causes cellular senescence and abnormal differentiation by inducing Yippee-like 3 expression in human keratinocytes.

Human steroid sulfatase (STS) is an enzyme that catalyzes the hydrolysis of dehydroepiandrosterone sulfate (DHEAS), estrone sulfate (E1S), and cholesterol sulfate. Abnormal expression of STS causes several diseases including colorectal, breast, and prostate cancer and refractory skin disease. In particular, accumulation of intracellular cholesterol sulfate by STS deficiency leads to a skin disorder with abnormal keratinization called X-linked ichthyosis (XLI).

Structure-Functional Analysis of Human Cytochrome P450 2C8 Using Directed Evolution.

The human genome includes four cytochrome P450 2C subfamily enzymes, and CYP2C8 has generated research interest because it is subject to drug-drug interactions and various polymorphic outcomes. To address the structure-functional complexity of CYP2C8, its catalytic activity was studied using a directed evolution analysis. Consecutive rounds of random mutagenesis and screening using 6-methoxy-luciferin produced two mutants, which displayed highly increased luciferase activity.

CCL8 mediates crosstalk between endothelial colony forming cells and triple-negative breast cancer cells through IL-8, aggravating invasion and tumorigenicity.

Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer with a poor prognosis for which no effective therapeutic measures are currently available. The present study aimed to investigate whether interactions with endothelial colony-forming cells (ECFCs) promote aggressive progression of TNBC cells. Herein, using an indirect co-culture system, we showed that co-culture increased the invasive and migratory phenotypes of both MDA-MB-231 TNBC cells and ECFCs.

Biological roles of cytochrome P450 1A1, 1A2, and 1B1 enzymes.

Human cytochrome P450 enzymes (CYPs) play a critical role in various biological processes and human diseases. CYP1 family members, including CYP1A1, CYP1A2, and CYP1B1, are induced by aryl hydrocarbon receptors (AhRs). The binding of ligands such as polycyclic aromatic hydrocarbons activates the AhRs, which are involved in the metabolism (including oxidation) of various endogenous or exogenous substrates.

Combined treatment with auranofin and trametinib induces synergistic apoptosis in breast cancer cells.

Auranofin is a gold complex used as an anti-rheumatic agent and may act as a potent anticancer drug against breast tumors. Trametinib is a specific mitogen-activated protein kinase inhibitor, approved for the treatment of metastatic melanoma. The aim of this study was to examine the synergistic effects of auranofin and trametinib on apoptosis in MCF-7 human breast cancer cells.

Synergistic Induction of Apoptosis by the Combination of an Axl Inhibitor and Auranofin in Human Breast Cancer Cells.

Axl receptor tyrosine kinase has been implicated in cancer progression, invasion, and metastasis in various cancer types. Axl overexpression has been observed in many cancers, and selective inhibitors of Axl, including R428, may be promising therapeutic agents for several human cancers, such as breast, lung, and pancreatic cancers. Here, we examined the cell growth inhibition mediated by R428 and auranofin individually as well as in combination in the human breast cancer cell lines MCF-7 and MDAMB- 231 to identify new advanced combination treatments for human breast cancer.

Characteristics of fecal metabolic profiles in patients with irritable bowel syndrome with predominant diarrhea investigated using H-NMR coupled with multivariate statistical analysis.

Background: Gut microbiota are known to be closely related to irritable bowel syndrome (IBS). However, not much is known about characteristic fecal metabolic profiles of IBS. We aimed to characterize fecal metabolites in patients with IBS with predominant diarrhea (IBS-D) using H-nuclear magnetic resonance ( H-NMR) spectroscopy.

CYP1B1 prevents proteasome-mediated XIAP degradation by inducing PKCε activation and phosphorylation of XIAP.

Cytochrome P450 1B1 (CYP1B1) is a key enzyme that catalyzes the metabolism of 17β-estradiol (E2) into catechol estrogens, such as 2-hydroxyestradiol (2-OHE2) and 4-hydroxyestradiol (4-OHE2). CYP1B1 is related to tumor formation and is over-expressed in a variety of cancer cells. In particular, CYP1B1 is highly expressed in hormone-related cancers such as breast cancer, ovarian cancer, or prostate cancer compared to other cancers.

G0/G1 Switch 2 Induces Cell Survival and Metastasis through Integrin-Mediated Signal Transduction in Human Invasive Breast Cancer Cells.

Human breast cancer cell line, MDA-MB-231, is highly invasive and aggressive, compared to less invasive cell line, MCF-7. To explore the genes that might influence the malignancy of MDA-MB-231, DNA microarray analysis was performed. The results showed that G0/G1 switch 2 (G0S2) was one of the most highly expressed genes among the genes upregulated in MDA-MB-231.

Combination treatment with auranofin and nutlin-3a induces synergistic cytotoxicity in breast cancer cells.

Auranofin is a gold complex categorized as an anti-rheumatic agent. Recently, several investigators suggested that auranofin may act as a potent anti-cancer drug for breast tumors. Nutlin-3a is a cis-imidazoline analog which prevents interaction between mouse double minute 2 homolog (MDM2) and the tumor suppressor p53.

Human steroid sulfatase enhances aerobic glycolysis through induction of HIF1α and glycolytic enzymes.

Human steroid sulfatase (STS) has been linked with poor prognosis in steroid-associated tumors and represents an important clinical target in cancers, yet the mechanism of STS-induced carcinogenesis remains unclear. To correlate STS with cancer metabolism, we determined the effects of STS on aerobic glycolysis. STS overexpression increased cellular levels of lactic acid, the final product of aerobic glycolysis.

CYP52A23 from Candida albicans and its Substrate Preference for Fatty Acid Hydroxylation.

The pathogenic fungus Candida albicans contains genes encoding five fatty acid hydroxylases belonging to the CYP52 family in its genome. Our previous study reported that CYP52A21 demonstrated typical omega-hydroxylation of lauric acid (Kim D, Cryle MJ, De Voss JJ, Ortiz de Montellano PR (2007) Arch Biochem Biophys 464, 213-220). Functional characterization of CYP52 fatty acid hydroxylases was studied, and their selectivity for hydroxylation was analyzed.

Adaptable Small Ligand of CYP1 Enzymes for Use in Understanding the Structural Features Determining Isoform Selectivity.

Although several families of compounds have been identified as scaffolds for inhibitors of the CYP1 family, the isoform selectivity determining structural features has not been fully clarified at the molecular interaction level. We studied the CYP1 isoform selectivity for stilbenoid inhibitors using integrated induced fit docking and molecular dynamics simulations. The hydrophobic interactions with the specific phenylalanine residues in the F helix are correlated with inhibitory potency in the CYP1 family.

Discovery of Ezrin Expression as a Potential Biomarker for Chemically Induced Ocular Irritation Using Human Corneal Epithelium Cell Line and a Reconstructed Human Cornea-like Epithelium Model.

Numerous studies have attempted to develop a new in vitro eye irritation test (EIT). To obtain more reliable results from EIT, potential new biomarkers that reflect eye irritation by chemicals must be identified. We investigated candidate biomarkers for eye irritation, using a proteomics approach.