Ginkgolic Acid Inhibits Proliferation and Migration of Glioblastoma Cells by Inducing Cell Cycle Arrest and Apoptosis

Abstract

Glioblastoma (GBM) is the most frequent and aggressive primary brain tumor with high mortality rate and poor prognosis. Ginkgolic acid (GA), a botanical component extracted from the leaves and seed coat of Ginkgo biloba L., presented various bioactivities including anti-tumor, neuroprotective, and anti-bacterial effects. However, the effects of GA on GBM cells were still unclear. In the study, GA was found to present effective inhibition on the cell viability and migration of GBM cells. Results of the Annexin V-FITC/PI staining and nucleus morphology assay revealed that apoptosis of GBM cells was triggered by GA treatment. By flow cytometry, real-time PCR and western blotting assay, cell cycle arrest at G0/G1 phase by GA treatment was shown with the downregulation of CCNA and CCNB. Further investigation validated that the intracellular reactive oxygen species was accumulated after GA treatment. Moreover, GA upregulated the phosphorylation of ERK and p38 MAPK. These results indicated that GA exhibited effective inhibition on cell proliferation and migration by inducing cell cycle arrest and apoptosis in GBM cells. Further, production of reactive oxygen species and MAPK signaling were involved in GA induced anti-GBM effects.