Abstract
Glioblastoma, the most aggressive and malignant form of glioma, appears to be resistant to various chemotherapeutic agents. Hence, approaches have been intensively investigated to targeti specific molecular pathways involved in glioblastoma development and progression. Aloe emodin is believed to modulate the expression of several genes in cancer cells. We aimed to understand the molecular mechanisms underlying the therapeutic effect of Aloe emodin on gene expression profiles in the human U87 glioblastoma cell line utilizing microarray technology. The gene expression analysis revealed that a total of 8,226 gene alterations out of 28,869 genes were detected after treatment with 58.6 μg/ml for 24 hours. Out of this total, 34 genes demonstrated statistically significant change (p<0.05) ranging from 1.07 to 1.87 fold. The results revealed that 22 genes were up-regulated and 12 genes were down-regulated in response to Aloe emodin treatment. These genes were then grouped into several clusters based on their biological functions, revealing induction of expression of genes involved in apoptosis (programmed cell death) and tissue remodelling in U87 cells (p<0.01). Several genes with significant changes of the expression level e.g. SHARPIN, BCAP31, FIS1, RAC1 and TGM2 from the apoptotic cluster were confirmed by quantitative real-time PCR (qRT-PCR). These results could serve as guidance for further studies in order to discover molecular targets for the cancer therapy based on Aloe emodin treatment.
Highlights
Glioblastoma (WHO grade IV) is the most common and most aggressive type of malignant brain tumour
We found that Aloe emodin significantly inhibits U87 cell proliferation in dose-dependent and time-dependent manners
This result is consistent with previous reports on inhibitory effects of Aloe emodin treatment in various human cancer cells such as hepatoma cells (Kuo et al, 2002), skin cancers (Wasserman et al, 2002), gastric cancers (Qin et al, 2010), leukaemic cells (Tabolacci et al, 2011) and breast cancer cells (Huang et al, 2013)
Summary
Glioblastoma (WHO grade IV) is the most common and most aggressive type of malignant brain tumour. Glioblastoma differs from other type of cancer due to the fact that it is rarely metastasize (Rich et al, 2005), the mortality rate is still nearly 100% and survival of patients are still less than 1 year after conventional treatment was used (Caffo et al, 2013). Current treatment for glioblastoma patients includes the use of a combination of surgery, radiotherapy and chemotherapy. Despite these advances in treatment, overall outcome of glioblastoma remains poor in patients (Wintner et al, 2011). Some of these treatments are quite expensive and highly toxic. New therapeutic agent with low cost and less toxicity need to be developed
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