Detail Information of Exogenous Modulation

General Information of Drug Transporter (DT)
DT ID DTD0089 Transporter Info
Gene Name SLC12A8
Transporter Name Cation-chloride cotransporter 9
Gene ID
84561
UniProt ID
A0AV02
Exogenous factors (drugs, dietary constituents, etc.) Modulation of This DT (EGM)

Chemical Compound

  DT Modulation1

 Hydrogen Peroxide co-treated with Theophylline results in increased expression of SLC12A8 protein [1]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation1

 Estradiol results in increased expression of SLC12A8 mRNA [29]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation1

 Cisplatin co-treated with jinfukang results in increased expression of SLC12A8 mRNA [14]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation1

 Valproic Acid affects the expression of SLC12A8 mRNA [34]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation2

 Valproic Acid results in increased expression of SLC12A8 mRNA [35]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation1

 Coumestrol co-treated with 2,3-bis(3'-hydroxybenzyl)butyrolactone results in decreased expression of SLC12A8 mRNA [2]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation1

 Benzo(a)pyrene affects the methylation of SLC12A8 promoter [24]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation2

 Benzo(a)pyrene results in decreased methylation of SLC12A8 5' UTR [24]

Regulation Mechanism

 Transcription Factor Info

  2,3-bis(3'-hydroxybenzyl)butyrolactone

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Coumestrol co-treated with 2,3-bis(3'-hydroxybenzyl)butyrolactone results in decreased expression of SLC12A8 mRNA [2]

Regulation Mechanism

 Transcription Factor Info

  abrine

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 abrine results in decreased expression of SLC12A8 mRNA [21]

Regulation Mechanism

 Transcription Factor Info

  aristolochic acid I

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 aristolochic acid I results in decreased expression of SLC12A8 mRNA [23]

Regulation Mechanism

 Transcription Factor Info

  bisphenol A

            3 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 bisphenol A co-treated with Fulvestrant results in decreased methylation of SLC12A8 gene [25]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation2

 bisphenol A results in decreased methylation of SLC12A8 gene [25]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation3

 bisphenol A results in increased expression of SLC12A8 mRNA [15]

Regulation Mechanism

 Transcription Factor Info

  Cadmium Chloride

            2 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Cadmium Chloride results in increased abundance of Cadmium which results in increased expression of SLC12A8 mRNA [26]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation2

 Cadmium Chloride results in increased expression of SLC12A8 mRNA [4]

Regulation Mechanism

 Transcription Factor Info

  CGP 52608

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 CGP 52608 promotes the reaction RORA protein binds to SLC12A8 gene [27]

Regulation Mechanism

 Transcription Factor Info

  chloroacetaldehyde

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 chloroacetaldehyde affects the expression of SLC12A8 mRNA [4]

Regulation Mechanism

 Transcription Factor Info

  chromium hexavalent ion

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 chromium hexavalent ion affects the expression of SLC12A8 mRNA [28]

Regulation Mechanism

 Transcription Factor Info

  entinostat

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 entinostat results in increased expression of SLC12A8 mRNA [13]

Regulation Mechanism

 Transcription Factor Info

  FR900359

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 FR900359 results in increased phosphorylation of SLC12A8 protein [30]

Regulation Mechanism

 Transcription Factor Info

  Fulvestrant

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 bisphenol A co-treated with Fulvestrant results in decreased methylation of SLC12A8 gene [25]

Regulation Mechanism

 Transcription Factor Info

  ICG 001

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 ICG 001 results in increased expression of SLC12A8 mRNA [11]

Regulation Mechanism

 Transcription Factor Info

  lead acetate

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 lead acetate results in increased expression of SLC12A8 mRNA [31]

Regulation Mechanism

 Transcription Factor Info

  Manganese

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 manganese chloride results in increased abundance of Manganese which results in increased expression of SLC12A8 mRNA [32]

Regulation Mechanism

 Transcription Factor Info

  manganese chloride

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 manganese chloride results in increased abundance of Manganese which results in increased expression of SLC12A8 mRNA [32]

Regulation Mechanism

 Transcription Factor Info

  Oxygen

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Oxygen deficiency results in decreased expression of SLC12A8 mRNA [4]

Regulation Mechanism

 Transcription Factor Info

  potassium chromate(VI)

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 potassium chromate(VI) results in increased expression of SLC12A8 mRNA [10]

Regulation Mechanism

 Transcription Factor Info

  sodium arsenite

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 sodium arsenite results in increased expression of SLC12A8 mRNA [10]

Regulation Mechanism

 Transcription Factor Info

  sulforaphane

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 sulforaphane results in increased expression of SLC12A8 mRNA [17]

Regulation Mechanism

 Transcription Factor Info

  Theophylline

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Hydrogen Peroxide co-treated with Theophylline results in increased expression of SLC12A8 protein [1]

Regulation Mechanism

 Transcription Factor Info

Mycotoxins

  Aflatoxin B1

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Aflatoxin B1 results in decreased methylation of SLC12A8 intron [22]

Regulation Mechanism

 Transcription Factor Info

Approved Drug

  Hydrogen Peroxide

            2 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Hydrogen Peroxide inhibits the expression of SLC12A8 [1]

  Estradiol

            2 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Estradiol inhibits the expression of SLC12A8 [2]

  Cyclosporine

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Cyclosporine increases the expression of SLC12A8 [3]

  Cidofovir

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Cidofovir affects the expression of SLC12A8 [4]

  Cisplatin

            2 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Cisplatin inhibits the expression of SLC12A8 [4]

  Ifosfamide

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Ifosfamide inhibits the expression of SLC12A8 [4]

  Acetaminophen

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Acetaminophen inhibits the expression of SLC12A8 [5]

  Valproic Acid

            3 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Valproic Acid inhibits the expression of SLC12A8 [6]

  Doxorubicin

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Doxorubicin inhibits the expression of SLC12A8 [7]

  Sunitinib

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Sunitinib increases the expression of SLC12A8 [8]

  Temozolomide

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Temozolomide inhibits the expression of SLC12A8 [9]

Drug Marketed but not Approved by US FDA

  Clodronic Acid

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Clodronic Acid inhibits the expression of SLC12A8 [4]

Drug in Phase 3 Trial

  Sulforafan

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Sulforafan increases the expression of SLC12A8 [17]

Drug in Phase 2 Trial

  MS-275

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 MS-275 increases the expression of SLC12A8 [13]

  Bisphenol A

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Bisphenol A increases the expression of SLC12A8 [15]

Drug in Phase 1 Trial

  Sodium arsenite

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Sodium arsenite increases the expression of SLC12A8 [10]

Drug in Preclinical Test

  (+)-JQ1

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 (+)-JQ1 inhibits the expression of SLC12A8 [12]

Investigative Drug

  Coumestrol

            2 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Coumestrol inhibits the expression of SLC12A8 [2]

Patented Pharmaceutical Agent

  ICG-001

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 ICG-001 increases the expression of SLC12A8 [11]

  GSK-J4

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 GSK-J4 inhibits the expression of SLC12A8 [16]

Natural Product

  Tobacco Smoke Pollution

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Tobacco Smoke Pollution increases the expression of SLC12A8 [19]

  Gallic Acid

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Gallic Acid inhibits the expression of SLC12A8 [20]

Traditional Medicine

  Jinfukang

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Jinfukang increases the expression of SLC12A8 [14]

Carcinogen

  Benzo(a)pyrene

            3 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Benzo(a)pyrene inhibits the expression of SLC12A8 [18]

  Cadmium

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Cadmium Chloride results in increased abundance of Cadmium which results in increased expression of SLC12A8 mRNA [26]

Regulation Mechanism

 Transcription Factor Info

  Nickel

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Nickel results in increased expression of SLC12A8 mRNA [33]

Regulation Mechanism

 Transcription Factor Info
References
1 Oxidative stress modulates theophylline effects on steroid responsiveness. Biochem Biophys Res Commun. 2008 Dec 19;377(3):797-802.
2 Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
3 Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
4 Transcriptomics hit the target: Monitoring of ligand-activated and stress response pathways for chemical testing. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):7-18.
5 Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
6 Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
7 Bringing in vitro analysis closer to in vivo: Studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
8 Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761.
9 Temozolomide induces activation of Wnt/beta-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278.
10 Gene expression changes in human lung cells exposed to arsenic, chromium, nickel or vanadium indicate the first steps in cancer. Metallomics. 2012 Aug;4(8):784-93.
11 Altering cancer transcriptomes using epigenomic inhibitors. Epigenetics Chromatin. 2015 Feb 24;8:9.
12 CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
13 Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
14 Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
15 Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
16 Inhibition of histone H3K27 demethylases selectively modulates inflammatory phenotypes of natural killer cells. J Biol Chem. 2018 Feb 16;293(7):2422-2437.
17 Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047.
18 Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297.
19 Integration of transcriptome analysis with pathophysiological endpoints to evaluate cigarette smoke toxicity in an in vitro human airway tissue model. Arch Toxicol. 2021 May;95(5):1739-1761.
20 Gene expression profile analysis of gallic acid-induced cell death process. Sci Rep. 2021 Aug 18;11(1):16743.
21 Integration of transcriptomics, proteomics and metabolomics data to reveal the biological mechanisms of abrin injury in human lung epithelial cells. Toxicol Lett. 2019;312:1-10.
22 Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018;121:214-223.
23 Integration of transcriptomic, proteomic and metabolomic data to reveal the biological mechanisms of AAI injury in renal epithelial cells. Toxicol In Vitro. 2021;70:105054.
24 Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017;8(1):1369-1391.
25 DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019;11(1):138.
26 Cadmium acute exposure induces metabolic and transcriptomic perturbations in human mature adipocytes. Toxicology. 2022;470:153153.
27 Identification of potential target genes of ROR-alpha in THP1 and HUVEC cell lines. Exp Cell Res. 2017;353(1):6-15.
28 Review of transcriptomic responses to hexavalent chromium exposure in lung cells supports a role of epigenetic mediators in carcinogenesis. Toxicol Lett. 2019;305:40-50.
29 17 beta-Estradiol Activates HSF1 via MAPK Signaling in ER alpha-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533.
30 Protein Kinase Signaling Networks Driven by Oncogenic Gq/11 in Uveal Melanoma Identified by Phosphoproteomic and Bioinformatic Analyses. Mol Cell Proteomics. 2023;22(11):100649.
31 Analysis of lead toxicity in human cells. BMC Genomics. 2012;13:344.
32 Using transcriptomic signatures to elucidate individual and mixture effects of inorganic arsenic and manganese in human placental trophoblast HTR-8/SVneo cells. Toxicol Sci. 2025;203(2):216-226.
33 Patients with atopic dermatitis have attenuated and distinct contact hypersensitivity responses to common allergens in skin. J Allergy Clin Immunol. 2015;135(3):712-20.
34 Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20.
35 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.

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