title: 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.
authors.affiliation: Laboratory of Pharmacognosy, Division of Pharmacognosy-Pharmacology, Faculty of Health Sciences, School of Pharmacy, Aristotle University of Thessaloniki, 541 24, Thessaloniki, Greece.
authors.forename: Diamanto
authors.initials: D
authors.lastname: Lazari
authors.affiliation: Medical School, Neurosurgical Institute, University of Ioannina, PO BOX 103, Neochoropoulo, Ioannina, Greece. alexiougrg@yahoo.gr.
authors.forename: George A
authors.initials: GA
authors.lastname: Alexiou
authors.affiliation: Laboratory of Biology, School of Medicine, University of Ioannina, Ioannina, Greece.|Division of Biomedical Research, IMBB-FORTH University Campus, Ioannina, Greece.
authors.forename: Georgios S
authors.initials: GS
authors.lastname: Markopoulos
authors.affiliation: Medical School, Neurosurgical Institute, University of Ioannina, PO BOX 103, Neochoropoulo, Ioannina, Greece.
authors.forename: Evrysthenis
authors.initials: E
authors.lastname: Vartholomatos
authors.affiliation: Laboratory of Pharmacognosy, Division of Pharmacognosy-Pharmacology, Faculty of Health Sciences, School of Pharmacy, Aristotle University of Thessaloniki, 541 24, Thessaloniki, Greece.|Department of Industrial Chemistry, Faculty of Natural Sciences, University of Tirana, Tirana, Albania.
authors.forename: Entela
authors.initials: E
authors.lastname: Hodaj
authors.affiliation: Zoology Laboratory Department of Biological Application and Technology, University of Ioannina, 45110, Ioannina, Greece.
authors.forename: Ieremias
authors.initials: I
authors.lastname: Chousidis
authors.affiliation: Zoology Laboratory Department of Biological Application and Technology, University of Ioannina, 45110, Ioannina, Greece.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Leonardos
authors.affiliation: Department of Anatomy-Histology-Embryology, Medical School, University of Ioannina, 45110, Ioannina, Greece.
authors.forename: Vasiliki
authors.initials: V
authors.lastname: Galani
authors.affiliation: Medical School, Neurosurgical Institute, University of Ioannina, PO BOX 103, Neochoropoulo, Ioannina, Greece.
authors.forename: Athanasios P
authors.initials: AP
authors.lastname: Kyritsis
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001932:Brain Neoplasms / Q000473:pathology*; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D005909:Glioblastoma / Q000473:pathology*; D006801:Humans; D012701:Serotonin / Q000494:pharmacology*; D015027:Zebrafish
chemical_list: D000970:Antineoplastic Agents; D012701:Serotonin; C114774:N-(p-coumaroyl)serotonin
keywords: Apoptosis; Glioma; N-(p-coumaroyl) serotonin