J Cancer 2015; 6(8):786-794. doi:10.7150/jca.12251
Could the Anti-Chaperone VER155008 Replace Temozolomide for Glioma Treatment
Brain Tumour North West, Faculty of Science and Technology, University of Central Lancashire, Preston, PR1 2HE. UK.
Shervington L, Patil H, Shervington A. Could the Anti-Chaperone VER155008 Replace Temozolomide for Glioma Treatment. J Cancer 2015; 6(8):786-794. doi:10.7150/jca.12251. Available from http://www.jcancer.org/v06p0786.htm
Cancer inducible molecular chaperone HSP90 is of great importance as an anticancer target. Proteomic analysis showed that inhibiting HSP90 by the geldanamycin derivative, 17-AAG elevated the expression of the co-chaperone Hsp70. In this study we used HSP90 selective inhibitor 17-AAG and HSP70/90 dual inhibitor, VER155008 (VER) in U87-MG glioma cells. miRNAs microarray technology was used to evaluate the efficacy of these inhibitory drugs compared with temozolomide (TMZ), used as a standard treatment for glioma. Microarrays data identified 154 differentially expressed miRNAs using stringent or unstringent parameters. 16 miRNAs were overlapped between treatments, 13 upregulated and one downregulated miRNA were overlapped between TMZ and VER. The miRNA target prediction software was used for these overlapped miRNAs and identified 6 of the 13 upregulated miRNAs target methyltransferase genes. The IC50, together with Akt and HSP70 and 90 protein level data favour VER and TMZ to 17-AAG, however due to the selectivity of VER to cancer cells as a potent antichaperon, it may be more favourable to the standard TMZ.
Keywords: HSP70, HSP90, miRNA, glioma cells, 17-AAG, VER (VER155008 ), TMZ