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Glioblastoma stem cells: a new target for metformin and arsenic trioxide.

Al's Comment:

 Sounds interesting in theory - but a clinical trial is needed to test it. Should be easy because both components are fda approved for other things.

Keep in mind arsenic at the wrong dose can be fatal.


Posted on: 04/23/2014

  J Biol Regul Homeost Agents. 2014 Jan-Mar;28(1):1-15.
Glioblastoma stem cells: a new target for metformin and arsenic trioxide.
Carmignani M1, Volpe AR1, Aldea M2, Soritau O3, Irimie A4, Florian IS5, Tomuleasa C6, Baritchii A5, Petrushev B2, Crisan G7, Valle G8.
Author information: 
1Laboratory of Pharmacology and Toxicologyy, Department of Life, Health and Environmental Sciences, University of L'Aquila, Coppito, Italy.
2Iuliu Hatieganu University of Medicine and Pharmacy, Cluj Napoca, Romania.
3Department of Immunology, Ion Chiricuta Comprehensive Cancer Center, Cluj Napoca, Romania.
4Departments of Surgery, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj Napoca, Romania.
5Neurosurgery, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj Napoca, Romania.
6Department of Medicine, Division of Gastroenterology and Hepatology, the Johns Hopkins University School of Medicine, Baltimore, MD, USA.
7Pharmaceutical Botany, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj Napoca, Romania.
8Nuclear Medicine Unit, Scientific Institute Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.
 
Abstract
The high malignancy of glioblastoma has been recently attributed to the presence, within the tumor, of glioblastoma stem cells (GSC) poorly responsive to chemo- and radiotherapy. Here, the potential employment of metformin and arsenic trioxide (ATO) in glioblastoma therapy is discussed focusing on their effects on GSC. Metformin exerts anticancer effects by primarily blocking the pivotal LKB1/AMPK/mTOR/S6K1 pathway-dependent cell growth, induces selective lethal effects on GSC by impairing the GSC-initiating spherogenesis and inhibits the proliferation of CD133+ cells, while having a low or null effect on differentiated glioblastoma cells and normal human stem cells. Metformin and ATO induce autophagy and apoptosis in glioma cells by inhibiting and stimulating the PI3K/Akt and the mitogen-activated protein kinase pathways, respectively. Both drugs promote differentiation of GSC into non-tumorigenic cells. In this regard, metformin acts via activation of the AMPK-FOXO3 axis, whereas ATO blocks the interleukin 6-induced promotion of STAT3 phosphorylation. Blood-brain barrier, easily crossed by metformin but not by ATO, undergoes important glioblastoma-induced alterations that increase its permeability, thus allowing ATO to distribute more into the glioblastoma bulk than in the normal brain parenchyma. A prompt clinical assessment of metformin and ATO in glioblastoma patients would represent a valid attempt to improve their survival. 
 
 PMID: 24750786 [PubMed - in process] 
 

 


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