Antitumor effects of Sweroside in human glioblastoma: its effects on mitochondrial mediated apoptosis, activation of different caspases, G0/G1 cell cycle arrest and targeting JNK/p38 MAPK signal pathways.

PURPOSE

Glioblastoma is one of the prevalent types of brain tumors and is responsible for significant number of deaths world over. Glioblastoma is often diagnosed at advanced stages and there are frequent relapses following chemotherapy. Herein, we examined the anticancer effects of a secoiridoid glycoside Sweroside, against a panel of glioblastoma cells.

METHODS

CCK8 assay was used to examine the anti-proliferative effects of this molecule. Αcridine orange (AO)/ethidium bromide (EB) and annexin V/propidium iodide (PI) staining assays were used to examine apoptotic cell death. Cell cycle analysis was performed by flow cytometry. The protein expression was examined by western blotting.

RESULTS

Sweroside inhibited the growth of the glioblastoma U251 cell with IC50 of 10 µM. However, Sweroside had low cytotoxic effects on the normal astrocytes cells with an IC50 of 100 µM. Sweroside exerted antiproliferative effects on the U251 glioblastoma cells by apoptotic cell death. This was concomitant with upregulation of apoptotic proteins such as caspase 3 and 9, and Bax expressions. Sweroside also induced arrest of the U251 cells at the G0/G1 phase of the cell cycle. Finally, Sweroside also blocked the JNK/p38 MAPK signal pathway concentration-dependently in U251 glioblastoma cells.

CONCLUSIONS

Taken together, these results suggest that Sweroside exerts potent anticancer effects on glioblastoma cells and may prove essential in the management of glioblastoma.