Purpose Glioblastoma multiforme (GBM) is the primary aggressive malignancy of the brain with poor outcome. Curcumin analogues are polyphenolic compounds as the bioactive substances extracted from turmeric. This study aims to investigate the anti-cancer effects of four curcumin analogues. Furthermore, the molecular mechanisms of dimethoxycurcumin in human gliomas were analyzed by Western blot. Materials and Methods Human LN229 and GBM8401 glioma cells were treated by four curcumin analogues with different number of methoxy groups. The cell viability, cell cycle, apoptosis, proliferation and ROS production of human gliomas were analyzed by flow cytometry. Moreover, the effects of four curcumin analogues on tumorigenesis of gliomas were conducted by wound healing assay and colony formation assay. Furthermore, the molecular mechanisms of dimethoxycurcumin in human gliomas were analyzed by Western blot. Results Our data showed that four different curcumin analogues including curcumin, bisdemethoxycurcumin, demethoxycurcumin, and dimethoxycurcumin promote sub-G1 phase, G2/M arrest, apoptosis, and ROS production in human glioma cells. Moreover, dimethoxycurcumin suppressed cell viability, migration, and colony formation, induction of sub-G1, G2/M arrest, apoptosis, and ROS production in glioma cells. Moreover, the mechanism of dimethoxycurcumin is ROS production to increase LC3B-II expression to induce autophagy. Furthermore, dimethoxycurcumin suppressed apoptotic marker, BCL-2 to promote apoptosis in LN229 and GBM8401 glioma cells. Conclusion Our study found that dimethoxycurcumin induced apoptosis, autophagy, ROS production and suppressed cell viability in human gliomas. Dimethoxycurcumin might be a potential therapeutic candidate in human glioma cells.

Purpose Glioblastoma multiforme is a highly malignant primary brain cancer with a poor prognosis. We recently reported that ARID4B could potentially serve as a biomarker associated with poor survival in glioma patients. However, the function of ARID4B in human gliomas remains unclear. The aim of this study is to investigate the molecular cell biology role of ARID4B in human glioma cells. Materials and Methods Gene Expression Omnibus (GEO) and Human Protein Atlas (HPA) datasets were analyzed for the expression of ARID4B in WHO pathological grading, overall survival and immunohistochemical staining. Using quantitative RT-PCR and Western blotting, those findings were confirmed in normal brain tissue and glioma cell lines. ARID4B knockdown was conducted via lentivirus-based transfection of small hairpin RNA in human glioma cells to investigate cell proliferation, cell cycle, and apoptosis. Results In the present study, our analysis of GEO datasets showed that ARID4B mRNA expression is higher in WHO grade IV tumors (n = 81) than in non-tumor control tissue (n = 23, P <0.0001). ARID4B knockdown suppressed glioma cell proliferation and induced G1 phase arrest via the PI3K/AKT pathway. It also increased expression of HDAC1 , leading to higher acetyl-p53 and acetyl-H3 levels and reduced glioma cell migration and invasion. These effects were mediated via downregulation of AKT pathway components, including p-mTOR, p-PI3K and p-AKT. ARID4B knockdown also led to downregulation of Cyclin D1, which increased apoptosis in human glioma cells. Conclusion These findings that ARID4B expression correlates positively with WHO pathologic grading in glioma. ARID4B knockdown suppresses PI3K/AKT signaling and induces apoptosis in human glioma cells. These results suggests that ARID4B acts as an oncogene in human gliomas.