Screening of the Prime bioactive compounds from Aloe vera as potential anti-proliferative agents targeting DNA.

BACKGROUND: Aloe vera extract and its bioactive compounds possess anti-proliferative properties against cancer cells. However, no detailed molecular mechanism of action studies has been reported. We have now employed a computational approach to scrutinize the molecular mechanism of lead bioactive compounds from Aloe vera that potentially inhibit DNA synthesis. METHODS: Initially, the anti-proliferative activity of Aloe vera extract was examined in human breast cancer cells (in vitro/in vivo). Later on, computational screening of bioactive compounds from Aloe vera targeting DNA was performed by molecular docking and molecular dynamics simulation. RESULTS: In-vitro and in-vivo studies confirm that Aloe vera extract effectively suppresses the growth of breast cancer cells without significant cytotoxicity towards non-cancerous normal immortal cells. Computational screening predicts that growth suppression may be due to the presence of DNA intercalating bioactive compounds (riboflavin, daidzin, aloin, etc.) contained in Aloe vera. MM/PBSA calculation showed that riboflavin has a higher binding affinity at the DNA binding sites compared to standard drug daunorubicin. CONCLUSIONS: These observations support the hypothesis that riboflavin may be exploited as an anti-proliferative DNA intercalating agent to prevent cancer and is worthy of testing for the management of cancer by performing more extensive pre-clinical and if validated clinical trials.

Oncogene AEG-1 promotes glioma-induced neurodegeneration by increasing glutamate excitotoxicity.

Aggressive tumor growth, diffuse tissue invasion, and neurodegeneration are hallmarks of malignant glioma. Although glutamate excitotoxicity is considered to play a key role in glioma-induced neurodegeneration, the mechanism(s) controlling this process is poorly understood. Astrocyte elevated gene-1 (AEG-1) is an oncogene that is overexpressed in several types of human cancers, including more than 90% of brain tumors. In addition, AEG-1 promotes gliomagenesis, particularly in the context of tumor growth and invasion, 2 primary characteristics of glioma. In the present study, we investigated the contribution of AEG-1 to glioma-induced neurodegeneration. Pearson correlation coefficient analysis in normal brain tissues and samples from glioma patients indicated a strong negative correlation between expression of AEG-1 and a primary glutamate transporter of astrocytes EAAT2. Gain- and loss-of-function studies in normal primary human fetal astrocytes and T98G glioblastoma multiforme cells revealed that AEG-1 repressed EAAT2 expression at a transcriptional level by inducing YY1 activity to inhibit CBP function as a coactivator on the EAAT2 promoter. In addition, AEG-1-mediated EAAT2 repression caused a reduction of glutamate uptake by glial cells, resulting in induction of neuronal cell death. These findings were also confirmed in samples from glioma patients showing that AEG-1 expression negatively correlated with NeuN expression. Taken together, our findings suggest that AEG-1 contributes to glioma-induced neurodegeneration, a hallmark of this fatal tumor, through regulation of EAAT2 expression.