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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).
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Last modified:
Mar 17, 2023
In our library since:
Mar 11, 2013
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20
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0
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http://dl.cm-uj.krakow.pl:8080/publication/3482
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| Edition name | Date |
|---|---|
| ZB-116988 | Mar 17, 2023 |
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