Auraptene Induces Apoptosis in Human Malignant Glioblastoma Cell Line Through Reactive Oxygen Species (ROS)

Glioblastoma multiforme (GBM) is the most aggressive type of brain tumor in adults, and represent one of the most challenging cancers tocontrol due to its aggressive nature. This study aimed to investigate the cytotoxic effects of a natural product, Auraptene, and the signaling pathways affected in a human malignant GBM (U87) cells. Materials and Methods: The Auraptene-induced ROS production in U87 cells evaluated by use of a cellular reactive oxygen species detection method. Changes of mRNA level of some essential genes involved in apoptosis were also evaluated in Auraptene-treated cells. Results: Our results demonstrated a significant decline in ROS production in the first 2, and 6 hours after treatment with Auraptene, however, ROS level increased in other incubation periods (8 and 24 hours). Interestingly,N-acetyl cysteine (NAC) markedly attenuated the Auraptene–induced ROS production and reversed Auraptene–induced cytotoxicity in 8 and 24 hours after treatment as well. Induction of apoptosis occurred in the first 24 and 48 hours in a concentration- and timedependentmanner. The qRT-PCR results indicated an up-regulation in p21, CXCL3 and a down-regulation in Cyclin D1 mRNA expression. Conclusion: In general this study showed an increase in ROS level is at least one of the mechanisms associated with Auraptene-induced toxicity on glioma cells. Also, the induction of apoptosis through Bax/Bcl-2 regulation and expression of genes involved in apoptosis initiation are other mechanisms by which Auraptene instigates its cytotoxic effects in U87 cells. Therefore, Auraptene could be utilized as a potential novel anti-GBM agent, after complementary studies.