β-asarone induces apoptosis and cell cycle arrest of human glioma U251 cells via suppression of HnRNP A2/B1-mediated pathway in vitro and in vivo

Abstract

HnRNP A2/B1 has been found to be an oncogenic protein strongly related to the growth of human glioma cells. Herein, β-asarone, the main component in the volatile oil of Acori tatarinowii Rhizoma, inhibited the cell viability, proliferation, and colony formation ability of U251 cells. Moreover, β-asarone induced apoptosis and cell cycle arrest at the G1 phase. Notably, β-asarone suppressed the expression of hnRNP A2/B1 and hnRNPA2/B1 overexpression remarkably reversed β-asarone-mediated apoptosis and cell cycle arrest. Importantly, β-asarone promoted the alternative splicing of Bcl-x by enhancing the ratio of Bcl-xS/Bcl-xL. Meanwhile, hnRNPA2/B1 overexpression mitigated the promoting effect of β-asarone on the alternative splicing of Bcl-x. β-asarone also regulated the level of the key proteins involved in the death receptor pathway and mitochondrial apoptosis pathway. Additionally, β-asarone modulated the cell cycle-related proteins p21, p27, Cdc25A, cyclin D, cyclin E, and CDK2. Finally, β-asarone inhibited tumor growth and induced apoptosis in nude mice bearing U251 tumor xenografts. β-asarone also suppressed the hnRNP A2/B1 expression, enhanced the expression of cleaved-caspase 3 and p27 and the ratio of Bcl-xS/Bcl-xL, and reduced the expression of CDK2 in U251 xenografts. Together, β-asarone-induced apoptosis and cell cycle arrest of U251 cells may be related to the suppression of hnRNPA2/B1-mediated signaling pathway.