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

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.