scholarly journals Dopamine is an aryl hydrocarbon receptor agonist

2020 ◽  
Vol 477 (19) ◽  
pp. 3899-3910
Author(s):  
Hyejin Park ◽  
Un-ho Jin ◽  
Keshav Karki ◽  
Arul Jayaraman ◽  
Clint Allred ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Aryl Hydrocarbon Receptor ◽  
Cancer Cells ◽  
Agonist Activity ◽  
Metabolizing Enzymes ◽  
Aryl Hydrocarbon ◽  
Pancreatic Cancer Cells ◽  
Aryl Hydrocarbon Receptor Agonist ◽  
Tryptophan Metabolites ◽  
High Concentrations

Tryptophan metabolites exhibit aryl hydrocarbon receptor (AhR) agonist activity and recent studies show that the phenylalanine metabolites serotonin and carbidopa, a drug used in treating Parkinson's disease, activated the AhR. In this study, we identified the neuroactive hormone dopamine as an inducer of drug-metabolizing enzymes CYP1A1, CYP1B1, and UGT1A1 in colon and glioblastoma cells and similar results were observed for carbidopa. In contrast, carbidopa but not dopamine exhibited AhR activity in BxPC3 pancreatic cancer cells whereas minimal activity was observed for both compounds in Panc1 pancreatic cancer cells. In contrast with a previous report, the induction responses and cytotoxicity of carbidopa was observed only at high concentrations (100 µM) in BxPC3 cells. Our results show that similar to serotonin and several tryptophan metabolites, dopamine is also an AhR-active compound.

scholarly journals Regulation of a long noncoding RNA MALAT1 by aryl hydrocarbon receptor in pancreatic cancer cells and tissues

2020 ◽  
Vol 532 (4) ◽  
pp. 563-569
Author(s):  
Ji-eun Lee ◽  
Sung-Gook Cho ◽  
Seong-Gyu Ko ◽  
Syed A. Ahrmad ◽  
Alvaro Puga ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Aryl Hydrocarbon Receptor ◽  
Cancer Cells ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Aryl Hydrocarbon ◽  
Pancreatic Cancer Cells

scholarly journals In Vitro Transformation of Chlorinated Parabens by the Liver S9 Fraction: Kinetics, Metabolite Identification, and Aryl Hydrocarbon Receptor Agonist Activity

2016 ◽  
Vol 64 (6) ◽  
pp. 650-654 ◽  
Author(s):  
Masanori Terasaki ◽  
Takeshi Wada ◽  
Satoshi Nagashima ◽  
Masakazu Makino ◽  
Hiro Yasukawa
Keyword(s):  
Aryl Hydrocarbon Receptor ◽  
Receptor Agonist ◽  
Metabolite Identification ◽  
Agonist Activity ◽  
Aryl Hydrocarbon ◽  
Aryl Hydrocarbon Receptor Agonist ◽  
S9 Fraction

scholarly journals Direct Assessment of Cumulative Aryl Hydrocarbon Receptor Agonist Activity in Sera from Experimentally Exposed Mice and Environmentally Exposed Humans

2010 ◽  
Vol 118 (5) ◽  
pp. 693-698 ◽  
Author(s):  
Jennifer J. Schlezinger ◽  
Pamela L. Bernard ◽  
Amelia Haas ◽  
Philippe Grandjean ◽  
Pal Weihe ◽  
...  
Keyword(s):  
Aryl Hydrocarbon Receptor ◽  
Receptor Agonist ◽  
Agonist Activity ◽  
Direct Assessment ◽  
Aryl Hydrocarbon ◽  
Aryl Hydrocarbon Receptor Agonist

Carbidopa is an activator of aryl hydrocarbon receptor with potential for cancer therapy

2017 ◽  
Vol 474 (20) ◽  
pp. 3391-3402 ◽  
Author(s):  
Jiro Ogura ◽  
Seiji Miyauchi ◽  
Kazumi Shimono ◽  
Shengping Yang ◽  
Sathisha Gonchigar ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Liver Cancer ◽  
Aryl Hydrocarbon Receptor ◽  
Cancer Cells ◽  
Inhibitory Effect ◽  
Anticancer Effect ◽  
Liver Cancer Cells ◽  
Aryl Hydrocarbon

Carbidopa is used with l-DOPA (l-3,4-dihydroxyphenylalanine) to treat Parkinson's disease (PD). PD patients exhibit lower incidence of most cancers including pancreatic cancer, but with the notable exception of melanoma. The decreased cancer incidence is not due to l-DOPA; however, the relevance of Carbidopa to this phenomenon has not been investigated. Here, we tested the hypothesis that Carbidopa, independent of l-DOPA, might elicit an anticancer effect. Carbidopa inhibited pancreatic cancer cell proliferation both in vitro and in vivo. Based on structural similarity with phenylhydrazine, an inhibitor of indoleamine-2,3-dioxygenase-1 (IDO1), we predicted that Carbidopa might also inhibit IDO1, thus providing a molecular basis for its anticancer effect. The inhibitory effect was confirmed using human recombinant IDO1. To demonstrate the inhibition in intact cells, AhR (aryl hydrocarbon receptor) activity was monitored as readout for IDO1-mediated generation of the endogenous AhR agonist kynurenine in pancreatic and liver cancer cells. Surprisingly, Carbidopa did not inhibit but instead potentiated AhR signaling, evident from increased CYP1A1 (cytochrome P450 family 1 subfamily A member 1), CYP1A2, and CYP1B1 expression. In pancreatic and liver cancer cells, Carbidopa promoted AhR nuclear localization. AhR antagonists blocked Carbidopa-dependent activation of AhR signaling. The inhibitory effect on pancreatic cancer cells in vitro and in vivo and the activation of AhR occurred at therapeutic concentrations of Carbidopa. Chromatin immunoprecipitation assay further confirmed that Carbidopa promoted AhR binding to its target gene CYP1A1 leading to its induction. We conclude that Carbidopa is an AhR agonist and suppresses pancreatic cancer. Hence, Carbidopa could potentially be re-purposed to treat pancreatic cancer and possibly other cancers as well.

scholarly journals Novel Aryl Hydrocarbon Receptor Agonist Suppresses Migration and Invasion of Breast Cancer Cells

PLoS ONE ◽  
2016 ◽  
Vol 11 (12) ◽  
pp. e0167650 ◽  
Author(s):  
Hamza Hanieh ◽  
Omar Mohafez ◽  
Villianur Ibrahim Hairul-Islam ◽  
Abdullah Alzahrani ◽  
Mohammad Bani Ismail ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Aryl Hydrocarbon Receptor ◽  
Cancer Cells ◽  
Receptor Agonist ◽  
Breast Cancer Cells ◽  
Migration And Invasion ◽  
Aryl Hydrocarbon ◽  
Aryl Hydrocarbon Receptor Agonist

scholarly journals Cholecystokinin and pancreatic cancer: the chicken or the egg?

2014 ◽  
Vol 306 (2) ◽  
pp. G91-G101 ◽  
Author(s):  
Jill P. Smith ◽  
Travis E. Solomon
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Intraepithelial Neoplasia ◽  
Human Pancreas ◽  
Cck Receptors ◽  
Pancreatic Cancer Cells ◽  
Endogenous Production ◽  
Pancreatic Proteases ◽  
Normal Human ◽  
High Concentrations

The gastrointestinal peptide cholecystokinin (CCK) causes the release of pancreatic digestive enzymes and growth of the normal pancreas. Exogenous CCK administration has been used in animal models to study pancreatitis and also as a promoter of carcinogen-induced or Kras-driven pancreatic cancer. Defining CCK receptors in normal human pancreas has been problematic because of its retroperitoneal location, high concentrations of pancreatic proteases, and endogenous RNase. Most studies indicate that the predominant receptor in human pancreas is the CCK-B type, and CCK-A is the predominant form in rodent pancreas. In pancreatic cancer cells and tumors, the role of CCK is better established because receptors are often overexpressed by these cancer cells and stimulation of such receptors promotes growth. Furthermore, in established cancer, endogenous production of CCK and/or gastrin occurs and their actions stimulate the synthesis of more receptors plus growth by an autocrine mechanism. Initially it was thought that the mechanism by which CCK served to potentiate carcinogenesis was by interplay with inflammation in the pancreatic microenvironment. But with the recent findings of CCK receptors on early PanIN (pancreatic intraepithelial neoplasia) lesions and on stellate cells, the question has been raised that perhaps CCK actions are not the result of cancer but an early driving promoter of cancer. This review will summarize what is known regarding CCK, its receptors, and pancreatic cancer, and also what is unknown and requires further investigation to determine which comes first, the chicken or the egg, “CCK or the cancer.”

Synergistic effects of retrovirus IFN-α gene transfer and gemcitabine on apoptosis of pancreatic cancer cells

2001 ◽  
Vol 120 (5) ◽  
pp. A615-A615
Author(s):  
M GORSCHLUETER ◽  
B SCHOETTKER ◽  
A MAERTEN ◽  
C ZISKE
Keyword(s):  
Pancreatic Cancer ◽  
Gene Transfer ◽  
Cancer Cells ◽  
Synergistic Effects ◽  
Pancreatic Cancer Cells

Standardized herbal extracts of Japanese Kampo medicine and their effects on human and murine pancreatic cancer cells

2019 ◽  
Author(s):  
K Kuchta ◽  
K Weimer ◽  
L Frank ◽  
H Rausch ◽  
V Ellenrieder ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Kampo Medicine ◽  
Herbal Extracts ◽  
Pancreatic Cancer Cells

IKK1 promotes G1 phase progression of pancreatic cancer cells by the transcriptional regulation of the F-box protein skp2

2005 ◽  
Vol 43 (05) ◽  
Author(s):  
G Schneider ◽  
D Saur ◽  
J Siveke ◽  
R Fritsch ◽  
RM Schmid
Keyword(s):  
Pancreatic Cancer ◽  
Transcriptional Regulation ◽  
Cancer Cells ◽  
G1 Phase ◽  
Pancreatic Cancer Cells ◽  
Phase Progression ◽  
F Box Protein

Knockdown or inhibition of CDK4 sensitizes pancreatic cancer cells to TRAIL-induced apoptosis

2005 ◽  
Vol 43 (05) ◽  
Author(s):  
M Retzer-Lidl ◽  
G Schneider ◽  
RM Schmid
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Pancreatic Cancer Cells ◽  
Induced Apoptosis
Sign in / Sign up

Export Citation Format

Share Document