Antiproliferative efficacy of elderberries and elderflowers (Sambucus canadensis) on glioma and brain endothelial cells under normoxic and hypoxic conditions

Elderberries are among the richest sources of antioxidant anthocyanins with health-promoting properties. As low circulating plasma antioxidant levels contribute to solid tumor malignancy, we assessed the antiproliferative properties of two Canadian elderberry cultivar extracts, 'Kent' and 'Scotia', against human brain tumor-derived cell line models and brain microvascular endothelial cells under both normoxic and hypoxic culture conditions. Elderberry, concentrated elderberry and elderflower extracts inhibited cell proliferation in a dose-dependent manner with berry extracts being more efficient. The antiproliferative effects resulted in cell cycle arrest through alterations in cell cycle checkpoint protein expression and in apoptosis. Anthocyanins and or rutin contents of the extracts efficiently inhibited cell proliferation alone or in synergy. Given brain tumors are characterized by high hypoxic areas which contribute to therapy resistance, this is the first evidence suggesting that Canadian elderberry extracts could efficiently target both the cancer and vascular compartments associated to brain tumor development.