Detail Information of Exogenous Modulation

General Information of Drug Transporter (DT)
DT ID DTD0057 Transporter Info
Gene Name ABCC11
Transporter Name Multidrug resistance-associated protein 8
Gene ID
85320
UniProt ID
Q96J66
Exogenous factors (drugs, dietary constituents, etc.) Modulation of This DT (EGM)

Chemical Compound

  DT Modulation1

 Fulvestrant inhibits the reaction Estradiol results in decreased expression of ABCC11 mRNA [2]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation2

 Tamoxifen inhibits the reaction Estradiol results in decreased expression of ABCC11 mRNA [2]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation1

 Tamoxifen inhibits the reaction Estradiol results in decreased expression of ABCC11 mRNA [2]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation1

 Valproic Acid results in decreased methylation of ABCC11 gene [23]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation1

 ABCC11 mRNA results in decreased abundance of Methotrexate [8]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation2

 ABCC11 mRNA results in decreased susceptibility to Methotrexate [8]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation3

 ABCC11 protein results in decreased susceptibility to Methotrexate [9]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation1

 ABCC11 protein results in decreased susceptibility to Fluorouracil [2]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation1

 Benzo(a)pyrene affects the methylation of ABCC11 promoter [17]

Regulation Mechanism

 Transcription Factor Info

  bisphenol A

            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 increased methylation of ABCC11 gene [18]

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 ABCC11 gene [19]

Regulation Mechanism

 Transcription Factor Info

  Chenodeoxycholic Acid

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

  DT Modulation1

 Triclosan co-treated with Glycochenodeoxycholic Acid co-treated with Deoxycholic Acid co-treated with Chenodeoxycholic Acid co-treated with Glycodeoxycholic Acid co-treated with Glycocholic Acid results in increased expression of ABCC11 mRNA [20]

Regulation Mechanism

 Transcription Factor Info

  Deoxycholic Acid

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

  DT Modulation1

 Triclosan co-treated with Glycochenodeoxycholic Acid co-treated with Deoxycholic Acid co-treated with Chenodeoxycholic Acid co-treated with Glycodeoxycholic Acid co-treated with Glycocholic Acid results in increased expression of ABCC11 mRNA [20]

Regulation Mechanism

 Transcription Factor Info

  Docetaxel

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

  DT Modulation1

 Docetaxel results in decreased susceptibility to Docetaxel which results in increased expression of ABCC11 mRNA [21]

Regulation Mechanism

 Transcription Factor Info

  Fluorodeoxyuridylate

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

  DT Modulation1

 ABCC11 protein results in decreased susceptibility to Fluorodeoxyuridylate [9]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation2

 ABCC11 protein results in increased export of Fluorodeoxyuridylate [9]

Regulation Mechanism

 Transcription Factor Info

  Fulvestrant

            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 increased methylation of ABCC11 gene [18]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation2

 Fulvestrant inhibits the reaction Estradiol results in decreased expression of ABCC11 mRNA [2]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation3

 Fulvestrant results in increased methylation of ABCC11 gene [18]

Regulation Mechanism

 Transcription Factor Info

  Glycochenodeoxycholic Acid

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

  DT Modulation1

 Triclosan co-treated with Glycochenodeoxycholic Acid co-treated with Deoxycholic Acid co-treated with Chenodeoxycholic Acid co-treated with Glycodeoxycholic Acid co-treated with Glycocholic Acid results in increased expression of ABCC11 mRNA [20]

Regulation Mechanism

 Transcription Factor Info

  Glycocholic Acid

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

  DT Modulation1

 Triclosan co-treated with Glycochenodeoxycholic Acid co-treated with Deoxycholic Acid co-treated with Chenodeoxycholic Acid co-treated with Glycodeoxycholic Acid co-treated with Glycocholic Acid results in increased expression of ABCC11 mRNA [20]

Regulation Mechanism

 Transcription Factor Info

  Glycodeoxycholic Acid

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

  DT Modulation1

 Triclosan co-treated with Glycochenodeoxycholic Acid co-treated with Deoxycholic Acid co-treated with Chenodeoxycholic Acid co-treated with Glycodeoxycholic Acid co-treated with Glycocholic Acid results in increased expression of ABCC11 mRNA [20]

Regulation Mechanism

 Transcription Factor Info

  methyleugenol

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

  DT Modulation1

 methyleugenol results in decreased expression of ABCC11 mRNA [14]

Regulation Mechanism

 Transcription Factor Info

  N-Nitrosopyrrolidine

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

  DT Modulation1

 N-Nitrosopyrrolidine results in decreased expression of ABCC11 mRNA [14]

Regulation Mechanism

 Transcription Factor Info

  Okadaic Acid

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

  DT Modulation1

 Okadaic Acid results in decreased expression of ABCC11 mRNA [22]

Regulation Mechanism

 Transcription Factor Info

  Pemetrexed

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

  DT Modulation1

 ABCC11 gene SNP affects the susceptibility to Pemetrexed [8]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation2

 ABCC11 mRNA results in decreased susceptibility to Pemetrexed [8]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation3

 ABCC11 protein results in decreased susceptibility to Pemetrexed [8]

Regulation Mechanism

 Transcription Factor Info

  Triclosan

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

  DT Modulation1

 Triclosan co-treated with Glycochenodeoxycholic Acid co-treated with Deoxycholic Acid co-treated with Chenodeoxycholic Acid co-treated with Glycodeoxycholic Acid co-treated with Glycocholic Acid results in increased expression of ABCC11 mRNA [20]

Regulation Mechanism

 Transcription Factor Info

Approved Drug

  Estradiol

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

  DT Modulation1

 Estradiol inhibits the expression of ABCC11 [2]

  Tamoxifen

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

  DT Modulation1

 Tamoxifen increases the expression of ABCC11 [2]

  Amiodarone

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

  DT Modulation1

 Amiodarone increases the expression of ABCC11 [3]

  Zidovudine

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

  DT Modulation1

 Zidovudine increases the expression of ABCC11 [4]

  Valproic Acid

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

  DT Modulation1

 Valproic Acid affects the expression of ABCC11 [5]

  Rifampin

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

  DT Modulation1

 Rifampin increases the expression of ABCC11 [6]

  Urethane

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

  DT Modulation1

 Urethane inhibits the expression of ABCC11 [7]

  Methotrexate

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

  DT Modulation1

 Methotrexate induces the activity of ABCC11 [8]

  Fluorouracil

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

  DT Modulation1

 Fluorouracil induces the activity of ABCC11 [9]

Drug in Phase 2 Trial

  Genistein

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

  DT Modulation1

 Genistein increases the expression of ABCC11 [10]

Investigative Drug

  Cyclic AMP

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

  DT Modulation1

 Cyclic adenosine monophosphate inhibits the transportation of Cyclic guanosine monophosphate by ABCC11 [1]

Affected Drug/Substrate

 Cyclic guanosine monophosphate Modulation Type Inhibition

Cell System

 LLC-PK1 vesicles-MRP8

Natural Product

  Methyleugenol

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

  DT Modulation1

 Methyleugenol inhibits the expression of ABCC11 [14]

Mycotoxins

  Aflatoxin B1

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

  DT Modulation1

 Aflatoxin B1 inhibits the expression of ABCC11 [11]

  DT Modulation2

 Aflatoxin B1 results in decreased methylation of ABCC11 intron [15]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation3

 Aflatoxin B1 results in increased methylation of ABCC11 gene [16]

Regulation Mechanism

 Transcription Factor Info

Acute Toxic Substance

  Cadmium

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

  DT Modulation1

 Cadmium inhibits the expression of ABCC11 [12]

Carcinogen

  Benzo(a)pyrene

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

  DT Modulation1

 Benzo(a)pyrene inhibits the expression of ABCC11 [14]

Health and Environmental Toxicant

  tris(1,3-dichloro-2-propyl)phosphate

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

  DT Modulation1

 tris(1,3-dichloro-2-propyl)phosphate inhibits the expression of ABCC11 [13]
References
1 Transport of bile acids, sulfated steroids, estradiol 17-beta-D-glucuronide, and leukotriene C4 by human multidrug resistance protein 8 (ABCC11). Mol Pharmacol. 2005 Feb;67(2):545-57.
2 ABCC11 expression is regulated by estrogen in MCF7 cells, correlated with estrogen receptor alpha expression in postmenopausal breast tumors and overexpressed in tamoxifen-resistant breast cancer cells. Endocr Relat Cancer. 2008 Mar;15(1):125-38.
3 Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
4 Differential gene expression in human hepatocyte cell lines exposed to the antiretroviral agent zidovudine. Arch Toxicol. 2014 Mar;88(3):609-23.
5 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.
6 Rifampin Regulation of Drug Transporters Gene Expression and the Association of MicroRNAs in Human Hepatocytes. Front Pharmacol. 2016 Apr 26;7:111.
7 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
8 ABCC11/MRP8 confers pemetrexed resistance in lung cancer. Cancer Sci. 2010 Nov;101(11):2404-10.
9 MRP8/ABCC11 directly confers resistance to 5-fluorouracil. Mol Cancer Ther. 2007 Jan;6(1):122-7.
10 Quantitative proteomics and transcriptomics addressing the estrogen receptor subtype-mediated effects in T47D breast cancer cells exposed to the phytoestrogen genistein. Mol Cell Proteomics. 2011 Jan;10(1):M110.002170.
11 Identification of early target genes of aflatoxin B1 in human hepatocytes, inter-individual variability and comparison with other genotoxic compounds. Toxicol Appl Pharmacol. 2012 Jan 15;258(2):176-87.
12 Using expression profiling to understand the effects of chronic cadmium exposure on MCF-7 breast cancer cells. PLoS One. 2013 Dec 20;8(12):e84646.
13 Defensive and adverse energy-related molecular responses precede tris (1, 3-dichloro-2-propyl) phosphate cytotoxicity. J Appl Toxicol. 2016 May;36(5):649-58.
14 Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297.
15 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.
16 Aflatoxin B1 induces persistent epigenomic effects in primary human hepatocytes associated with hepatocellular carcinoma. Toxicology. 2016 Mar 28;350-352:31-9.
17 Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017;8(1):1369-1391.
18 DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019;11(1):138.
19 Identification of potential target genes of ROR-alpha in THP1 and HUVEC cell lines. Exp Cell Res. 2017;353(1):6-15.
20 Dataset on transcriptomic profiling of cholestatic liver injury induced by food additives and a cosmetic ingredient. Data Brief. 2021;38:107373.
21 L-type calcium channel blockers reverse docetaxel and vincristine-induced multidrug resistance independent of ABCB1 expression in human lung cancer cell lines. Toxicol Lett. 2010 Feb 15;192(3):408-18.
22 A multi-omics approach to elucidate okadaic acid-induced changes in human HepaRG hepatocarcinoma cells. Arch Toxicol. 2024;98(9):2919-2935.
23 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.

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