Metabolomic dynamics of the arsenic-transformed bronchial epithelial cells and the derived cancer stem-like cells

Fu, Yao; Bi, Zhuoyue; Li, Lingzhi; Wadgaonkar, Priya; Qiu, Yiran; Almutairy, Bandar; Zhang, Wenxuan; Seno, Akimasa; Thakur, Chitra; Chen, Fei

doi:10.7150/ijbs.67314

Cited by 9 publications

(5 citation statements)

References 32 publications

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“…As expected, AHR is the most enriched pathway in this analysis, followed by pathways of oxidative stress, renal cell carcinoma, Hippo and non-Hippo, ATM dependent DNA damage, and lipid metabolism for LDL, HDL and TG (Figure 5 A, bottom panel). The effect of As 3+ and AHR on lipid metabolism supports our recent metabolomic study showing that As 3+ enhances lipids biosynthesis and catabolism 26 .…”

Section: Resultssupporting

confidence: 85%

Disruption of the tumor suppressor-like activity of aryl hydrocarbon receptor by arsenic in epithelial cells and human lung cancer

Fu¹,

Bi²,

Ji³

et al. 2023

Int. J. Biol. Sci.

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As the most classic and extensively studied transcription factor in response to environmental toxic chemicals, the human aryl hydrocarbon receptor (AHR) has been implicated in mediating some oncogenic responses also. Limited information is available, however, on whether arsenic, a widely presented environmental carcinogen, can regulate AHR to exert its carcinogenic activity. Through chromatin immunoprecipitation and sequencing (ChIP-seq), CRISPR-Cas9 gene editing, RNA-seq, and immunohistochemistry (IHC), in this report we provided evidence showing that arsenic enforces TGFβ and other oncogenic signaling pathways in bronchial epithelial cells through disrupting the tumor suppressor-like activity of AHR. AHR is normally enriched on a number of oncogenic genes in addition to the known phase I/II enzymes, such as genes in TGFβ and Nrf2 signaling pathways and several known oncogenes. Arsenic treatment substantially reduced the binding of AHR on these genes followed by an increased expression of these genes. CRISPR-Cas9-based knockout of AHR followed by RNA-seq further demonstrated increased expression of the TGFβ signaling and some oncogenic signaling pathway genes in the AHR knockout cells. IHC studies on human tissue samples revealed that normal human lung tissues expressed high level of AHR. In contrast, the AHR expression was diminished in the lung cancer tissues. Accordingly, the data from this study suggest that AHR has tumor suppressor-like activity for human lung cancer, and one of the carcinogenic mechanisms of arsenic is likely mediated by the inhibition of arsenic on the tumor suppressor-like activity of AHR.

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Section: Resultssupporting

confidence: 85%

Disruption of the tumor suppressor-like activity of aryl hydrocarbon receptor by arsenic in epithelial cells and human lung cancer

Fu¹,

Bi²,

Ji³

et al. 2023

Int. J. Biol. Sci.

Self Cite

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“…In a study on an Aβ25-35-induced mice model, 4-week administration of deoxyuridine, among other effects, reduced mitochondrial damage in the hippocampus and oxidative stress in the serum and brain, as well as apoptosis in primary mice hippocampal cells [ 74 ]. Another study showed that exposure to iAs influences the biosynthesis of nucleotides, and an increased level of deoxyuridine in human bronchial epithelial cells BEAS-2B was observed [ 75 ].…”

Section: Discussionmentioning

confidence: 99%

Analysis of Relationships between Metabolic Changes and Selected Nutrient Intake in Women Environmentally Exposed to Arsenic

Sijko-Szpańska,

Kozłowska

2024

Metabolites

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Nutrients involved in the metabolism of inorganic arsenic (iAs) may play a crucial role in mitigating the adverse health effects associated with such exposure. Consequently, the objective of this study was to analyze the association between the intake levels of nutrients involved in iAs metabolism and alterations in the metabolic profile during arsenic exposure. The study cohort comprised environmentally exposed women: WL (lower total urinary arsenic (As), n = 73) and WH (higher As, n = 73). The analysis included urinary untargeted metabolomics (conducted via liquid chromatography–mass spectrometry) and the assessment of nutrient intake involved in iAs metabolism, specifically methionine, vitamins B2, B6, and B12, folate, and zinc (based on 3-day dietary records of food and beverages). In the WL group, the intake of all analyzed nutrients exhibited a negative correlation with 5 metabolites (argininosuccinic acid, 5-hydroxy-L-tryptophan, 11-trans-LTE4, mevalonic acid, aminoadipic acid), while in the WH group, it correlated with 10 metabolites (5-hydroxy-L-tryptophan, dihyroxy-1H-indole glucuronide I, 11-trans-LTE4, isovalerylglucuronide, 18-oxocortisol, 3-hydroxydecanedioic acid, S-3-oxodecanoyl cysteamine, L-arginine, p-cresol glucuronide, thromboxane B2). Furthermore, nutrient intake demonstrated a positive association with 3 metabolites in the WL group (inosine, deoxyuridine, glutamine) and the WH group (inosine, N-acetyl-L-aspartic acid, tetrahydrodeoxycorticosterone). Altering the intake of nutrients involved in iAs metabolism could be a pivotal factor in reducing the negative impact of arsenic exposure on the human body. This study underscores the significance of maintaining adequate nutrient intake, particularly in populations exposed to arsenic.

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“…UCSC genome browser. Fu et al, 2022 [16] In GT, the most common omics and frequently used are transcriptomics, proteomics, and metabonomics or metabolomics. Transcriptomics is utilized to elucidate the mechanism of action.…”

Section: Gao Et Al 2022 [15]mentioning

confidence: 99%

“…The hypermethylation of CSE1L and TRRAP revealed a distinct route (direct P53 effector) linked to the individual DNMT1a polymorphism and provided the first proof of As-associated DNA methylation in connection to the expression of the ATR, ATF7IP, TPM3, and UBE2J2 genes. Fu et al [16] discovered that cells treated with As 3 had a significant suppression of all metabolites in the mitochondrial tricarboxylic acid cycle. These findings could lead to more accurate descriptions of the role of As in molecular carcinogenesis.…”

Section: Metalsmentioning

confidence: 99%

State of the Art of Genomic Technology in Toxicology: A Review

Recio-Vega

Facio-Campos

Hernández-González

et al. 2023

IJMS

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The rapid growth of genomics techniques has revolutionized and impacted, greatly and positively, the knowledge of toxicology, ushering it into a “new era”: the era of genomic technology (GT). This great advance permits us to analyze the whole genome, to know the gene response to toxicants and environmental stressors, and to determine the specific profiles of gene expression, among many other approaches. The aim of this work was to compile and narrate the recent research on GT during the last 2 years (2020–2022). A literature search was managed using the PubMed and Medscape interfaces on the Medline database. Relevant articles published in peer-reviewed journals were retrieved and their main results and conclusions are mentioned briefly. It is quite important to form a multidisciplinary taskforce on GT with the aim of designing and implementing a comprehensive, collaborative, and a strategic work plan, prioritizing and assessing the most relevant diseases, so as to decrease human morbimortality due to exposure to environmental chemicals and stressors.

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Metabolomic dynamics of the arsenic-transformed bronchial epithelial cells and the derived cancer stem-like cells

Cited by 9 publications

References 32 publications

Disruption of the tumor suppressor-like activity of aryl hydrocarbon receptor by arsenic in epithelial cells and human lung cancer

Disruption of the tumor suppressor-like activity of aryl hydrocarbon receptor by arsenic in epithelial cells and human lung cancer

Analysis of Relationships between Metabolic Changes and Selected Nutrient Intake in Women Environmentally Exposed to Arsenic

State of the Art of Genomic Technology in Toxicology: A Review

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