Prof. Mehmet Haberal is presented with The Award of The Spanish Order of The Civil Merit (Cruz de Official) by His Majesty King Felipe VI, King of Spain.
We are honored to announce that Prof. Dr. Seza Özen who is the member of Honorary Advisory Board of JBACHS has already won the Aziz Sancar Science Award of TUSEB.
We are happy to announce that The Journal of Basic and Clinical Health Sciences (JBACHS) is indexed by the Emerging Sources Citation Index since November 2017, and indexed by the Ulakbim-TR since 2017.
Journal of Basic and Clinical Health Sciences 2020 , Vol 4 , Issue 3
Repositioning of Metformin: Anticancer Agent for Hypoxic Neuroblastoma Cells
Seniz Inanc Surer1,Feriha Toksoz2,Serdar Bayrak3,Hanife Ecenur Meco4,Tolga Sever4,Yasemin Basbinar5,Hatice Nur Olgun6
1Dokuz Eylul University, Institute of Health Sciences, Department of Medical Biochemistry, Izmir, Turkey
2Dokuz Eylul Technology Development Zone, Tailor of Science Innovation Biotechnology Inc, Izmir, Turkey
3Dokuz Eylul University, Faculty of Medicine, Department of Cardiovascular Surgery, Izmır, Turkey
4Dokuz Eylul University, Institute of Health Sciences, Department of Translational Oncology, Izmır, Turkey
5Dokuz Eylul University, Institute of Oncology, Department of Translational Oncology, Izmır, Turkey
6Dokuz Eylul University, Institute of Oncology, Department of Pediadric Oncology, Izmır, Turkey
DOI : 10.30621/jbachs.2020.1373 Objectives: Neuroblastoma is an extracranial solid tumor of early childhood that has a hypoxic environment. VEGF and HIFs molecules play a role in adaptation to this microenvironment. Hypoxic microenvironment leads to poor prognosis and inadequate treatment of neuroblastoma. Metformin has been shown to inhibit tumor growth, might be a potential chemotherapeutic agent. The anti-cancer activity of Metformin on SH-SY5Y cells are not fully elucidated. The aim of this study is to determine the anti-cancer effect of Metformin on SH-SY5Y cells and to elucidate its molecular action mechanism in hypoxia/normoxia.

Patients and Methods: SH-SY5Y cells were exposed to increasing doses of Metformin. The viability of SH-SY5Y cells was evaluated using the real time xCELLigence RTCA system. Migration of SH-SY5Y cells was determined using wound healing. The effect of metformin on mRNA and protein expression levels was evaluated using Real-time PCR and Western Blot, respectively.

Results: Metformin was observed to significantly reduce the viability of SH-SY5Y cells. Metformin treatment reduced migration of SH-SY5Y cells. In addition, Metformin treatment significantly reduced mRNA expression of HIF-1α, PDK-1 and VEGF-A in SH-SY5Y cells under normoxia and hypoxia. In hypoxia condition, protein expression of HIF-1α and VEGF-A decreased after Metformin administration on SH-SY5Y cells. Protein expression of PDK-1 was observed to decrease in both normoxia and hypoxia conditions on SH-SY5Y cells.

Conclusion: In this study, the anti-cancer effect of Metformin on SH-SY5Y cells was determined. Metformin has been observed as inhibitor of migration in SH-SY5Y. Metformin treatment has been shown to reduce gene and protein levels of HIF-1α and target molecules in neuroblastoma cells. Keywords : neuroblastoma, metformin, hypoxia, HIF-1α, VEGF-A, PDK-1