Serotonin receptors, novel targets of sulforaphane identified by proteomic analysis in Caco-2 cells

Mastrangelo, Lina, Cassidy, Aedin, Mulholland, Francis, Wang, Wei and Bao, Yongping ORCID: https://orcid.org/0000-0002-6425-0370 (2008) Serotonin receptors, novel targets of sulforaphane identified by proteomic analysis in Caco-2 cells. Cancer Research, 68 (13). pp. 5487-5491.

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Abstract

Cancer chemopreventive activity of sulforaphane has been predominantly associated with its ability to induce phase II detoxification enzymes. In the present study, novel targets of sulforaphane were identified and characterized using a proteomics approach. Two-dimensional gel electrophoresis and mass spectrometry were used to produce protein profiles of human colon adenocarcinoma Caco-2 cells treated with 5 μmol/L sulforaphane for 48 h and control cells (0.05% DMSO). Gel comparisons showed the down-regulation to undetectable level of the serotonin receptor 5-HT3 after sulforaphane treatment. In addition, Aldo-keto reductase and d-dopachrome decarboxylase were also differentially expressed in control and treated cell extracts. To elucidate two-dimensional gel findings, the neurotransmitter receptors 5-HT3A, 5-HT1A, 5-HT2C, and the serotonin reuptake transporter were analyzed using Western blotting. Results showed a decrease of neurotransmitter receptors in a dose-dependent manner after sulforaphane treatment. Moreover, after exposure of Caco-2 cells to sulforaphane, nicotinic acetylcholine receptor protein level was increased. These findings suggested a potential effect of sulforaphane on serotonin release. Activation of neurotransmitter receptors followed by initiation of cyclic AMP signaling might be crucial events in colon carcinoma progression. Thus, the effect of sulforaphane may help to elucidate signaling pathways serotonin-mediated in colon cancer and lead to development of potential novel therapeutic agents.

Item Type: Article
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
Faculty of Science > School of Biological Sciences
UEA Research Groups: Faculty of Medicine and Health Sciences > Research Groups > Nutrition and Preventive Medicine
Faculty of Medicine and Health Sciences > Research Groups > Cardiovascular and Metabolic Health
Faculty of Medicine and Health Sciences > Research Groups > Cancer Studies
Faculty of Medicine and Health Sciences > Research Centres > Lifespan Health
Faculty of Medicine and Health Sciences > Research Centres > Metabolic Health
Depositing User: EPrints Services
Date Deposited: 25 Nov 2010 11:10
Last Modified: 13 Nov 2023 16:51
URI: https://ueaeprints.uea.ac.uk/id/eprint/13213
DOI: 10.1158/0008-5472.CAN-07-6171

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