Apoptotic and antiproliferative effects of amantadine and rimantadine in glioblastoma cells

Introduction: Glioblastoma (GBM) is a highly invasive tumor, which exhibits a poor response to standard chemotherapeutic agents. Amantadine, an anti-influenza A with anti-Parkinson’s effect, inhibits cell proliferation and induces apoptosis in hepatocellular cancer cells. Rimantadine, a derivative of amantadine with comparable effect on influenza, also improves symptoms of Parkinson’s disease. Objectives: The present study aimed to investigate apoptotic and antiproliferative effects of amantadine and rimantadine in two GBM cell lines, A172 and U-87 MG. Materials and Methods: Cell viability was measured by methyl thiazolyl tetrazolium assays. Cell apoptosis, cell proliferation, and cell cycle analysis were determined by flow cytometry using Annexin V/7-aminoactinomycin D, carboxyfluorescein diacetate succinimidyl ester, and propidium iodide with RNase staining, respectively. Results: Rimantadine demonstrated more cytotoxic effect than amantadine in both GBM cell lines. Rimantadine at 500 µM increased the percentage of early and late apoptosis of GBM cells, while amantadine at the same concentration induced the late apoptosis only in U-87 MG cells. Amantadine and rimantadine at 250-500 µM suppressed cell proliferation only in U-87 MG cells. Furthermore, 500 µM of both drugs induced G0/G1 arrest in U-87 MG cells. Conclusion: Amantadine and rimantadine induce apoptosis and inhibit proliferation through G0/G1 arrest; however, rimantadine shows higher toxicity, suggesting the greater therapeutic potential of rimantadine for GBM.