Basic and Clinical Neuroscience Journal
مجله علوم اعصاب پایه و بالینی
BCN
Medical Sciences
http://bcn.iums.ac.ir
137
journal137
2008-126X
2228-7442
10.32598/bcn
en
jalali
1396
4
1
gregorian
2017
7
1
8
4
online
1
fulltext
en
The Role of Protein Kinase B Signaling Pathway in Anti-cancer Effect of Rolipram on Glioblastoma Multiforme: An In Vitro Study
Cellular and molecular Neuroscience
Cellular and molecular Neuroscience
Original
Original
<p style="text-align: justify;"><strong>Introduction:</strong> The mechanism of putative cytotoxicity of 4-[3-(cyclopentyloxy)-4-methoxyphenyl]-2-pyrrolidone (rolipram), a specific phosphodiesterase-4 (PDE4) inhibitor, on glioblastoma multiforme (GBM) is almost unknown. This study aimed to investigate the role of protein kinase B (Akt) pathway in <a name="OLE_LINK1">the cytotoxic effect of rolipram on human GBM U87 MG cell line and tumor-initiating cells (TICs) isolated from patient's GBM specimen</a>.</p>
<p style="text-align: justify;"><strong>Methods: </strong>TICs were characterized by using flow cytometry and quantitative real-time PCR. The cells were treated with rolipram at inhibitory concentration of 50% (IC50) in the presence or absence of SC79 (4µg/mL), a specific AKT activator, for 48 hours. The cell viability and apoptosis were measured by MTT assay and TUNEL staining, respectively. The relative expression of Phospho-Akt (Ser473), matrix metalloproteinase 2 (MMP2), and vascular endothelial growth factor A (VEGF<sub>A</sub>) were detected using Western blotting.</p>
<p style="text-align: justify;"><strong>Results:</strong> The findings showed that rolipram could suppress cell viability in both U87MG and TICs, dose-dependently. Interestingly, the rolipram-induced cytotoxicity was significantly reduced in the presence of SC79. Nevertheless, in rolipram-treated cells, the pretreatment with SC79 significantly led to increase in U87 MG cells and TICs apoptosis and decrease in viability of U87 MG cells but not TICs relative to corresponding control. In U87 MG and TICs, rolipram-induced reduction of Phospho-Akt (Ser473) and MMP2 levels were significantly suppressed by SC79.</p>
<p style="text-align: justify;"><strong>Conclusion:</strong> There is a cell type-specific mechanism of anti-proliferative action of rolipram on GBM cells. The reduction of intracellular level of MMP2 but not VEGF<sub>A</sub> by rolipram is conducted through the inhibition of Akt signal. Rolipram-induced apoptosis is mediated via Akt dependent/independent mechanisms.</p>
Glioblastoma multiforme, Rolipram, SC79, U87 MG cell line, Tumor-initiating cells, Akt signal
325
336
http://bcn.iums.ac.ir/browse.php?a_code=A-10-983-1&slc_lang=en&sid=1
Sara
Ramezani
s.ramezanislp@gmail.com
13700319475328460010913
13700319475328460010913
No
Neuroscience Research Center, Department of Neurology, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran.
Mahmoudreza
Hadjighassem
13700319475328460010914
13700319475328460010914
No
Department of Neuroscience, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Nasim
Vousooghi
13700319475328460010915
13700319475328460010915
No
Department of Neuroscience, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Mansour
Parvaresh
13700319475328460010916
13700319475328460010916
No
Department of Neurosurgery, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
Farshid
Arbabi
13700319475328460010917
13700319475328460010917
No
Department of Oncology, Faculty of Medical Sciences, Zahedan University of Medical Sciences, Zahedan, Iran.
Naser
Amini
13700319475328460010918
13700319475328460010918
No
Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran.
Mohammad Taghi
Joghataei
mt.joghataei@yahoo.com
13700319475328460010919
13700319475328460010919
Yes
Department of Neuroscience, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.