| In vitro: |
| J Interferon Cytokine Res. 1998 Jun;18(6):423-8. | | Serotonin derivative, N-(p-coumaroyl) serotonin, inhibits the production of TNF-alpha, IL-1alpha, IL-1beta, and IL-6 by endotoxin-stimulated human blood monocytes.[Pubmed: 9660250 ] | We have reported that N-(p-coumaroyl) serotonin (CS) and its derivatives with antioxidative activity are present in safflower seeds.
METHODS AND RESULTS:
As reactive oxygen species (ROS) are implicated in the signaling of lipopolysaccharide (LPS), we examined whether CS has a suppressive effect on inflammatory cytokine generation from human monocytes in vitro. CS at 50-200 microM reduced tumor necrosis factor (TNF), interleukin-1 (IL-1), and IL-6 activities in the culture supernatants from LPS-stimulated human blood monocytes without cytotoxicity. ELISA assay revealed that the production of TNF-alpha, IL-1alpha, IL-1beta, and IL-6 was inhibited by CS. Northern blot analysis showed that LPS-induced expression of these cytokine mRNA in monocytes was suppressed by CS. NF-kappaB activation was also inhibited by CS.
CONCLUSIONS:
These findings indicate that CS has a suppressive effect on proinflammatory cytokine production from monocytes, and this effect is based in part on the suppression of cytokine mRNA expression through inhibition of NF-kappaB activation. | | J Neurooncol. 2017 May;132(3):373-381. | | N-(p-coumaroyl) serotonin inhibits glioblastoma cells growth through triggering S-phase arrest and apoptosis.[Pubmed: 28365838 ] | Glioblastoma is the most common and most malignant primary brain tumor with a median survival of 15 months. N-(p-coumaroyl) serotonin (CS) is an indole alkaloid with antioxidant, cardioprotective effects after ischemia and antitumor activity. In the present study we sought to determine whether could exert cytotoxic and cytostatic effects in glioma cells in vitro.
METHODS AND RESULTS:
CS was tested for toxicity in zebrafish. We investigated the effect of CS in U251MG and T98G glioblastoma cell lines. Viability and proliferation of the cells were examined with trypan blue exclusion assay and the xCELLigence system. Cell cycle, activation of caspase-8, mitochondrial membrane potential and CD24/CD44/CD56/CD15/CD71 expression were tested with flow cytometry. Treatment with CS significantly reduced cell viability in both cell lines tested. Induction of cell death and cell cycle arrest at G2/M and S-phase was confirmed with flow cytometry in both cell lines. CS produced significant higher activity of caspase-8 compared to control. After treatment with CS there was a dose-dependent increase in CD15 and CD71 expression, whereas there was no change in CD24/CD44/CD56 expression in both cell lines. The zebrafish mortality on the fifth post fertilization day was zero for even 1 mM of CS concentration.
CONCLUSIONS:
The treatment of glioblastoma cell lines with CS may represent a novel strategy for targeting glioblastoma. Further studies are obviously needed to elucidate the complete mechanism of its antitumor activity. |
|
Cell. 2018 Jan 11;172(1-2):249-261.e12. doi: 10.1016/j.cell.2017.12.019.IF=36.216(2019)
Cell Metab. 2020 Mar 3;31(3):534-548.e5. doi: 10.1016/j.cmet.2020.01.002.IF=22.415(2019)
Mol Cell. 2017 Nov 16;68(4):673-685.e6. doi: 10.1016/j.molcel.2017.10.022.IF=14.548(2019)
ACS Nano. 2018 Apr 24;12(4): 3385-3396. doi: 10.1021/acsnano.7b08969.IF=13.903(2019)
Nature Plants. 2016 Dec 22;3: 16206. doi: 10.1038/nplants.2016.205.IF=13.297(2019)
Sci Adv. 2018 Oct 24;4(10): eaat6994. doi: 10.1126/sciadv.aat6994.IF=12.804(2019)
