Serotonin Receptors, Novel Targets of Sulforaphane Identified by Proteomic Analysis in Caco-2 Cells

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 Mmol/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-HT 3 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-HT 3A , 5-HT 1A , 5-HT 2C , 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. [Cancer Res 2008;68(13):5487-91]

Molecular Targets of Dietary Phenethyl Isothiocyanate and Sulforaphane for Cancer Chemoprevention

“…Thus, SFN could sensitize cancer cells to apoptosis through DR5 upregulation which presents another potential mechanism of chemoprevention (83,84). Using proteomics approach, recently some novel targets of SFN were identified and characterized (85). Human colon adenocarcinoma cell (Caco-2) was treated with 5 μM SFN for 48 h and serotonin receptor 5-HT was downregulated to undetectable levels as compared to the controls (85).…”

“…Using proteomics approach, recently some novel targets of SFN were identified and characterized (85). Human colon adenocarcinoma cell (Caco-2) was treated with 5 μM SFN for 48 h and serotonin receptor 5-HT was downregulated to undetectable levels as compared to the controls (85). It was suggested that the activation of neurotransmitter receptors followed by initiation of cyclic AMP signaling might be crucial events in colon carcinoma progression.…”

Synergy between sulforaphane and selenium in protection against oxidative damage in colonic CCD841 cells

“…Other potential targets include kinases, transcriptional factors, transporters and receptors [21][22][23][24]. Since both Nrf2 and TrxR-1 can play dual roles in cancer [25][26][27][28] glutamine, penicillin (100 U/ml) and streptomycin (100µg/ml) under 5% CO 2 in air at 37 o C.…”

Anti-mitogenic and apoptotic effects of 5-HT1B receptor antagonist on HT29 colorectal cancer cell line

“…b Apoptotic HT29 cell after incubation with 5-HT 1A antagonist (5 M) for 48 h. c Apoptotic HT29 cell after incubation with 5-HT 1B antagonist (5 M) for 48 h. d Comparison of apoptotic index between three test groups and negative control; *P < 0.05; **P < 0.01 increases in patients with cancer, comprising 25% of this sub-population (Huerta et al 2006;Pezzella et al 2001). It seems plausible that introducing phytochemicals which have the most interactions with speciWc monoamine receptors (expressed highly in colorectal cancer tissues) may initiate new approaches in control of this malignancy (Mastrangelo et al 2008). There is ongoing debate about whether antidepressant medications may increase or decrease the risk of colon cancer.…”