The effect of telomerase template antagonist GRN163L on Bone-Marrow-Derived rat mMesenchymal stem cells is reversible and associated with altered expression of cyclin d1, cdk4 and cdk6
Author
Tokcaer-Keskin, Z.
Dikmen, Z. G.
Ayaloglu-Butun, F.
Gultekin, S.
Gryaznov, S. M.
Akcali, K. C.
Date
2010Source Title
Stem Cell Reviews and Reports
Print ISSN
1550-8943
Publisher
Springer Science+Business Media
Volume
6
Issue
2
Pages
224 - 233
Language
English
Type
ArticleItem Usage Stats
99
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Abstract
Telomerase activity is essential for the continued growth and survival of malignant cells, therefore inhibition of this activity presents an attractive target for anti-cancer therapy. The telomerase inhibitor GRN163L, was shown to inhibit the growth of cancer cells both in vitro and in vivo. Mesenchymal stem cells (MSCs) also show telomerase activity in maintaining their self-renewal; therefore the effects of telomerase inhibitors on MSCs may be an issue of concern. MSCs are multipotent cells and are important for the homeostasis of the organism. In this study, we sought to demonstrate in vitro effects of GRN163L on rat MSCs. When MSCs were treated with 1 μM GRN163L, their phenotype changed from spindle-shaped cells to rounded ones and detached from the plate surface, similar to cancer cells. Quantitative-RT-PCR and immunoblotting results revealed that GRN163L holds MSCs at the G1 state of the cell cycle, with a drastic decrease in mRNA and protein levels of cyclin D1 and its cdk counterparts, cdk4 and cdk6. This effect was not observed when MSCs were treated with a mismatch control oligonucleotide. One week after GRN163L was removed, mRNA and protein expressions of the genes, as well as the phenotype of MSCs returned to those of untreated cells. Therefore, we concluded that GRN163L does not interfere with the self-renewal and differentiation of MSCs under short term in vitro culture conditions. Our study provides additional support for treating cancers by administrating GRN163L without depleting the body's stem cell pools. © 2010 Springer Science+Business Media, LLC.
Keywords
Cdk4Cdk6
Cyclin D1
GRN163L
Mesenchymal stem cells
Telomerase
Cdk4 protein, rat
Cdk6 protein, mouse
Cyclin D1
Cyclin dependent kinase 4
Cyclin dependent kinase 6
GRN163L peptide
Oligonucleotide
Telomerase
Permalink
http://hdl.handle.net/11693/22313Published Version (Please cite this version)
http://dx.doi.org/10.1007/s12015-010-9124-7Collections
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