Potent anti-glioblastoma effect of 4-methylthio-3-butenyl isothiocyanate from Raphanus sativus and antioxidant activity

Abstract

ABSTRACT Several scientific researchers have focused on biological activities of edible plants such as radish. However, there are no researches on the anticancer effect of this plant in human glioblastoma. Thus, aims of this study were to evaluate the phytochemical composition, antioxidant and anticancer activities of Raphanus sativus bulbs aqueous and methanol extracts against U-87 MG cells. Five phenol compounds were found in aqueous extract using HPLC-DAD with syringic acid followed by protocatechuic acid, gallic acid, p-coumaric acid and cirsilineol. The DPPH, ABTS, OH radical, iron (II) chelation and FRAP assays exhibited that aqueous extract shows high antioxidant activity. The chemical composition analysis of the methanol extract using GC-MS showed that 4-methylthio-3-butenyl isothiocyanate (raphasatin) was the most abundant compound (20%). Cytotoxicity assessment by MTT method showed that methanol extract exhibited a significant cytotoxicity to U-87 MG cells with IC50 at 241.35 ± 15.21 µg/mL after 72 h while no effect was noted for aqueous extract. Dis-adhesion assay of the extracts as well as of raphasatin was assessed using different protein matrices (fibronectin, fibrinogen and poly-L-lysine) and the anti-proliferative effect was performed using doxorubicin as positive control. Methanol extract showed a high ability to inhibit cell adhesion to the used protein matrices with IC50 of 20.46 ± 2.52; 12.23 ± 1.41 and 16.21 ± 1.92 µg/mL, respectively. Moreover, raphasatin strongly inhibited tumor cell adhesion with IC50 of 0.63 ± 0.09; 1.27 ± 0.18 and 0.95 ± 0.12 µg/mL, respectively. In addition, it totally blocked the proliferation of cancer cells at a dose of 0.5 µg/mL after 4 days of incubation. These data demonstrate, for the first time, the protective effect of R. sativus methanol extract and its major compound, 4-methylthio-3-butenyl isothiocyanate against U-87 MG cancer cells. Raphasatin may represent an innovative and promising tool for human glioblastoma treatment.