Abstract
β-asarone, the main component in the volatile oil of Acori tatarinowii Rhizoma, has been found to possess antitumor activity. However, its effect and mechanisms against tumor invasion and epithelial–mesenchymal transition (EMT) are still unclear. In this study, no or less cytotoxicity was caused by β-asarone within 0–120 μM in human glioma U251 cells for 48 h. β-asarone (30 and 60 μM) inhibited the migration of U251 cells in the wound healing assay, suppressed the invasion of U251 cells in the Boyden chamber invasion assay, and inhibited the adhesion of U251 cells onto the Matrigel. Moreover, β-asarone suppressed EMT with the up-regulation of E-cadherin and the down-regulation of vimentin. HnRNP A2/B1, a well-characterized oncogenic protein, was shown at a high basal level in U251 cells and β-asarone reduced hnRNP A2/B1 expression in a concentration and time-dependent way. Importantly, hnRNP A2/B1 overexpression significantly counteracted the inhibition of β-asarone on the migration, invasion, and adhesion of U251 cells and reversed the modulation of EMT markers by β-asarone. Additionally, β-asarone decreased the MMP-9 and p-STAT3 in U251 cells, which was also reversed by hnRNP A2/B1 overexpression. Together, our results suggest that hnRNP A2/B1 may be a potential molecular target underlying the inhibitory effect of β-asarone on invasion and EMT in glioma cells.
Highlights
Brain tumors are one of the most common malignant tumors and are generally associated with a dismal prognosis and poor quality of life
We found that the inhibitory effect of β-asarone on the invasion (Figure 5C) and the expression of matrix metalloproteinases (MMPs)-9 and p-STAT3 (Figure 7B) was alleviated in U251 cells transfected with the vector only
Our results demonstrated that β-asarone reduced the expression of MMP-9 and p-STAT3 in U251 cells, while overexpression of hnRNP A2/B1 mitigated this effect of β-asarone
Summary
Brain tumors are one of the most common malignant tumors and are generally associated with a dismal prognosis and poor quality of life. The death rates have increased slightly for cancers of the brain and nervous system in both men and women. According to the data of 2015, the leading cause of cancer death among men below the age of 40 is brain and other nervous system tumors, and among woman below the age of 20 [1]. Gliomas are the most malignant type of brain tumor and are characterized by rapid growth, highly invasiveness, and enhanced angiogenesis [2]. A growing body of evidence has demonstrated that hnRNP A2/B1 is a novel oncogenic protein and is overexpressed in various tumors, including breast [4], pancreatic [5], liver [6], gastric [7], and lung carcinoma cells [8].
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