N-(p-coumaroyl) serotonin inhibits glioblastoma cells growth through triggering S-phase arrest and apoptosis

Abstract

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. 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. 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.

Anti-Tumor Activity of Cembranoid-Type Diterpenes Isolated from Nicotiana tabacum L.

“…To further explore the mechanism of α-CBD on hepatocellular carcinoma cells, the cell cycle and gene expression in HepG2 cells were detected. The results of flow cytometry demonstrated that α-CBD inhibited the proliferation of hepatocarcinoma cells at the S phase, which is consistent with the results of previous research showing that other antitumor compounds can induce G2/M arrest in human cancer cells [28,29]. Transcriptome profiling demonstrated that these differential genes are related to cell attachment, cell migration, mitosis, cell cycle, DNA strand extension in DNA replication, growth factor binding, protein localization, metal ion transition, cell death, programmed cell death, apoptosis progression, the apoptosis pathway, ubiquitin transferase activity, endoplasmic reticulum signaling pathway, and protein transport, all of which can promote apoptosis.…”

The Past, Present and Future of Flow Cytometry in Central Nervous System Malignancies

“…Our research group has been working towards novel therapeutics of GBM, which are based on natural products. Specifically, on the basis of experimental results that include FC methodologies, we have found that difluoromethylornithine (DFMO) [ 96 ] as well as the natural substances moschamine [ 97 ], n-p-coumaroyl-serotonin [ 98 ], and deglucohellebrin [ 99 ] exhibit significant antiglioma activity in vitro and low cytotoxity in vivo, as shown in a zebrafish embryo model.…”

“…DNA content analysis revealed several mechanisms of action for different antiglioma agents. For example, N-(p-coumaroyl)-serotonin resulted in both S and G2/M phase arrest, moschamine resulted mostly in S phase arrest and deglucohellebrin in G2/M phase arrest [ 97 , 98 , 99 ]. Several other studies have used in DNA content analysis quantification in several CNSM treatments, revealing, among others, the antiglioma effects of curcumin [ 100 ], quercetin [ 101 ], glycyrrhizic acid [ 102 ], and palbociclib [ 103 ].…”

Safflower Seed Extract Attenuates the Development of Osteoarthritis by Blocking NF-κB Signaling

“…Safflower seeds contain various flavonoids including serotonin, N-(p-coumaroyl) serotonin, N-feruloyl serotonin, luteolin, and luteolin-7-O-glucoside. However, N-(pcoumaroyl) serotonin and N-feruloyl serotonin are the most abundant flavonoids in safflower seed, and they have been used to treat cancer, cardiovascular diseases, and obesity [21,24,25,[35][36][37]. p-Coumaroyl serotonin and N-feruloyl serotonin are used to treat diabetes [36].…”

“…Serotonin, a flavonoid compound, is present as N-(p-coumaroyl) serotonin and N-feruloyl serotonin in safflower seeds. N-Feruloyl serotonin reduces the oxidation of low-density lipoproteins associated with the inflammatory processes of atherosclerosis [18], whereas N-(p-coumaroyl) serotonin has been used to prevent and treat bone diseases, cardiovascular diseases, glioma, and obesity [24][25][26]. N-(p-Coumaroyl) serotonin has been demonstrated to reduce oxidation and suppress inflammatory cytokine expression by inhibiting the NF-κB signaling pathway [27].…”