A DNA METHYLTRANSFERASE INHIBITOR RG108 POTENTIATES

A DNA METHYLTRANSFERASE INHIBITOR RG108 POTENTIATES NGFINDUCED NEURITE OUTGROWTH OF PC-12 Adh CELLS
Elif Kaya, Selin Engür, Miriş Dikmen
Anadolu University, Faculty of Pharmacy, Department of Pharmacology, Eskişehir,
TURKEY
Epigenetic refers to the reversible regulation of various genomic function that occur without a
change in the DNA sequence and mediated through changes in DNA methylation which can be
an alternative approach in the neurodegenerative diseases treatment. RG108 (N-phthaloyl-ltryptophan) is a novel non-nucleoside small-molecule DNA methyltransferase-1 inhibitor that
blocks the active site of the enzyme with low cytotoxicity.
In this study, related with neurite outgrowth, beta-III tubulin activity was determined by Alexa
Fluor® 488 secondary antibody on flow cytometer. Subsequently, growth associated protein 43
(GAP-43) and beta-III tubulin (TUBB3) mRNA expression levels were investigated at different
concentrations (10 and 100 nM) of RG108, alone or combined with 100 nM NGF, on PC-12
Adh cell line.
We found that depending on the increasing concentrations of RG108 in a combination with 100
nM NGF induced active beta-tubulin III levels on flow cytometry. Depending on concentration,
GAP-43 and TUBB3 mRNA expression levels increased almost 2.5 fold according to the
control group. In conclusion, DNA methyltransferase inhibitor RG108 may hold promise in
neurodegenerative diseases therapy. This study was founded as a part of Anadolu University
Scientific Research Project No:1501S004.
Key words: RG108, neurite outgrowth, PC-12 Adh, GAP-43, TUBB3.