Abstract
Identification of novel therapeutics in glioblastoma remains crucial due to the devastating and infiltrative capacity of this malignancy. The current study was aimed to appraise effect of arsenic trioxide (ATO) in U87MG cells. The results demonstrated that ATO induced apoptosis and impeded proliferation of U87MG cells in a dosedependent manner and also inhibited classical NF-κB signaling pathway. ATO further upregulated expression of Bax as an important proapoptotic target of NF-κB and also inhibited mRNA expression of survivin, c-Myc and hTERT and suppressed telomerase activity. Moreover, ATO significantly increased adhesion of U87MG cells and also diminished transcription of NF-κB down-stream targets involved in cell migration and invasion, including cathepsin B, uPA, MMP-2, MMP-9 and MMP-14 and suppressed proteolytic activity of cathepsin B, MMP-2 and MMP-9, demonstrating a possible mechanism of ATO effect on a well-known signaling in glioblastoma dissemination. Taken together, here we suggest that ATO inhibits survival and invasion of U87MG cells possibly through NF-κB-mediated inhibition of survivin and telomerase activity and NF-κB-dependent suppression of cathepsin B, MMP-2 and MMP-9.
Highlights
Tumors of the central nervous system (CNS) are usually highly devastating because they are difficult to treat and may cause disability or death
arsenic trioxide (ATO) significantly increased adhesion of U87MG cells and diminished transcription of NF-κB down-stream targets involved in cell migration and invasion, including cathepsin B, Urokinase plasminogen activator (uPA), matrix metalloproteases (MMPs)-2, MMP-9 and MMP-14 and suppressed proteolytic activity of cathepsin B, MMP-2 and MMP-9, demonstrating a possible mechanism of ATO effect on a well-known signaling in glioblastoma dissemination
Here we suggest that ATO inhibits survival and invasion of U87MG cells possibly through NF-κB-mediated inhibition of survivin and telomerase activity and NF-κB-dependent suppression of cathepsin B, MMP-2 and MMP-9
Summary
Tumors of the central nervous system (CNS) are usually highly devastating because they are difficult to treat and may cause disability or death. Among these tumors, astrocytic gliomas pose particular challenges because of being the most common intracranial malignant tumors in humans, tendency toward malignancy, rate of infiltration, and the lack of effective therapy (Rao, 2003). Grade IV, known as glioblastoma multiforme (GBM), is among the most lethal, highly invasive and least effectively-treated solid tumors in human. Devising more efficacious curative remedies that target tumor cell spread and invasion in GBM remains of main priority
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
