Abstract
Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor in adults. In recent studies, the efficacy of suberoylanilide hydroxamic acid (SAHA) has been investigated for GBM. We explored the effects of two exploratory compounds, the histone deacetylase SAHA and the natural product andrographolide, on Uppsala 87 Malignant Glioma (U-87 MG) cell migration and viability in comparison with the clinically used therapeutic agent temozolomide (TMZ). We used the electric cell–substrate impedance sensing (ECIS) system to monitor the migration of U-87 MG cells after treatment with various concentrations of these compounds. Moreover, we used the Alamar blue assay and western blotting to observe the concentration-dependent changes in the viability and apoptosis of U-87 MG cells. Our results demonstrated that both SAHA and andrographolide (10–300 μM) significantly inhibited GBM cell migration in a concentration-dependent manner, and 10 μM SAHA and 56 μM andrographolide demonstrated remarkable inhibitory effects on U-87 MG migration. Western blotting indicated that compared with TMZ, both SAHA and andrographolide induced higher expression levels of apoptosis-related proteins, such as caspase-3, BAX, and PARP in U-87 MG cells. Furthermore, all three drugs downregulated the expression of the antiapoptotic protein Bcl-2. In conclusion, SAHA and andrographolide showed exceptional results in inhibiting cell migration and motility. The ECIS wound healing assay is a powerful technique to identify and screen potential therapeutic agents that can inhibit cancer cell migration.
Highlights
Glioblastoma multiforme (GBM) is the most common and aggressive type of brain tumor in humans [1]
We investigated the cytotoxic effects of TMZ, suberoylanilide hydroxamic acid (SAHA), and andrographolide on migration of human glioblastoma Uppsala 87 Malignant Glioma (U-87 MG) cells through a label-free and noninvasive method, namely electric cell–substrate impedance sensing (ECIS)
Cells displayed shrunken morphology and other gross features after their exposure to 300 μM TMZ, 30 μM SAHA, or 30 μM andrographolide. These cytotoxic responses, including the decrease in adherent cell number and the increase in cell clumps, were even noticeable when U-87 MG cells were exposed to higher concentrations (>30 μM) of SAHA or andrographolide
Summary
Glioblastoma multiforme (GBM) is the most common and aggressive type of brain tumor in humans [1]. Among all cancers, it is one of the most challenging malignancies to treat in oncology [2]. Patients with GBM have an almost 100% mortality rate with a median survival of 14 months despite highly aggressive regimens consisting of maximal surgical resection, external beam radiation therapy, and adjuvant temozolomide (TMZ) chemotherapy. The very high mortality rate is due to the rapid proliferation and invasion of GBM and its resistance to conventional cancer therapy. Clinical toxicity is observed in almost 20% of patients treated with TMZ, and improved survival of 2 years is observed in
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