antitumor activity and mechanism study of riluzole and its derivatives

To explore novel antitumor agents with high efficiency and low toxicity, riluzole alkyl derivatives (4a-4i) were synthesized. their anti-proliferative activities against hela, hepg2, sp2/0, and mcf-7 cancer cell lines were assessed by the cck-8 assay and compared with human normal liver (lo2) cells. most of them showed potent cytotoxic effects against four human tumor cell lines and low toxic to lo2 cells. in particular, 2-(n-ethylamine)-6-trifluoromethoxybenzothiazole (4a) showed a ic50 value of 7.76 μmol/l in hela cells and was found to be nontoxic to lo2 cells up to 65 μmol/l. furthermore, flow cytometry indicated that 4a could induce remarkable early apoptosis and g2/m cell cycle arrest in hela cells. it also impaired the migration ability of hela cells in wound healing assays. western blot results demonstrated that 4a suppressed bcl-2 protein expression but increased the level of bax in hela cells, and elevated the bax/bcl-2 expression ratio. these new findings suggest that 4a exhibited beneficially anticervical cancer effect on hela cells by inducing hela cell apoptosis.