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Title: Effect of farnesyltransferase inhibitor R115777 on inhibition of the proliferation and on apoptosis induction in acute and chronic myeloid leukemia

Abstract:

Presented study tries to elucidate if the use of the of the CAAX-peptide binding site of farnesyl:protein transferase inhibitor (R115777), alone or in combination with other inhibitors as LY294002 (kinase PI3K inhibitor) and geldanamycine derivative 17AAG (heat shock protein inhibitor), leads to the proliferation rate decrease and apoptosis induction in U-937 and K-562 cell lines, corresponding to acute and chronic myeloid leukemia, respectively. The preliminary “ex vivo” investigations involved also a pool of mononuclear cells isolated from AML patients blood.The number of viable cells was evaluated with Trypan blue staining and proliferative potential using BrdU incorporation test, while apoptosis was assessed by enzymatic activity of caspase-3 and terminal dUTP nick-end labeling of DNA (TUNEL). The obtained results show that anticancer activity of R115777 can be enhanced by using it in combination with other drugs that reduce the activity of the main pro-survival pathway, such as LY294002 or 17AAG. The concentration of the individual inhibitors can be reduced, so that they only slow down the proliferative potential, and yet, the combination of inhibitors is still able to efficiently induce apoptosis. Our results show also that combination of R115777 + 17AAG has very promising anticancer activity directed against leukemic cells. In all experiments we observed that U937 cells (represent AML) were more sensitive to individual inhibitors, as well as their combinations, comparing with K562 cells (represent CML).

Place of publishing:

Kraków

Level of degree:

2 - studia doktoranckie

Degree discipline:

hematologia

Degree grantor:

Uniwersytet Jagielloński. Collegium Medicum. Wydział Lekarski.

Promoter:

Piotr Laidler

Date issued:

2011

Format:

application/pdf

Identifier:

oai:dl.cm-uj.krakow.pl:3482

Call number:

ZB-116988

ControlNumberVIRTUA:

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Language:

pol

Access rights:

tylko w bibliotece

Location of original object:

Biblioteka Medyczna Uniwersytetu Jagiellońskiego- Collegium Medicum

Object collections:

Last modified:

Oct 21, 2019

In our library since:

Mar 11, 2013

Number of object content hits:

9

Number of object content views in PDF format

7

All available object's versions:

http://dl.cm-uj.krakow.pl:8080/publication/3482

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ZB-116988 Oct 21, 2019
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