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Rapamycin enhances dimethyl sulfoxide-mediated growth arrest in human myelogenous leukemia cells


Lalić, Hrvoje; Lukinović-Škudar, Vesna; Banfić, Hrvoje; Višnjić, Dora
Rapamycin enhances dimethyl sulfoxide-mediated growth arrest in human myelogenous leukemia cells // The Annual Symposium of the Croatian Physiological Society with International Participation - Abstract Book
Zagreb: University of Zagreb School of Medicine, 2012. (predavanje, međunarodna recenzija, sažetak, znanstveni)


Naslov
Rapamycin enhances dimethyl sulfoxide-mediated growth arrest in human myelogenous leukemia cells

Autori
Lalić, Hrvoje ; Lukinović-Škudar, Vesna ; Banfić, Hrvoje ; Višnjić, Dora

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
The Annual Symposium of the Croatian Physiological Society with International Participation - Abstract Book / - Zagreb : University of Zagreb School of Medicine, 2012

Skup
The Annual Symposium of the Croatian Physiological Society with International Participation

Mjesto i datum
Zagreb, Hrvatska, 14-16.09.2012

Vrsta sudjelovanja
Predavanje

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
rapamycin; DMSO; acute myeloid leukemia

Sažetak
Introduction: The pharmacological inhibitors of phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway have been proposed in the treatment of leukemia based on their antiproliferative effects, but their possible role in differentiation therapy is less explored. Dimethyl sulfoxide (DMSO) is a potent inducer of granulocytic differentiation of acute myeloid leukemia (AML) lines. The aim of the present study was to test for the possible synergistic effects of rapamycin and DMSO on growth arrest and differentiation of AML. Materials and Methods: Myeloblastic (AML-M2) HL- 60, promyelocytic (AML-M3) NB4, monocytic (AML-M5) U937, immature (AML-M6) KG-1, and erythro- megakaryocytic K562 cells were maintained in exponential growth and differentiated in the presence of DMSO (0.6 or 1.25%). The number of viable cells was quantified using a hemocytometer. The expression of differentiation markers and the cell cycle distribution of propidium iodide- labeled cells were determined by FACS analyses. Cell morphology was evaluated on May-Grunwald- Giemsa-stained cytospin preparations. The level of phosphorylated (Thr389) and total p70 S6 Kinase (p70 S6K) in cell lysates was determined by Western blot analysis. Results: Western blot analysis demonstrated that rapamycin (20 nM) completely reduced the level of Thr389-phosphorylated p70 S6K. When applied for 96 h, rapamycin (20nM) alone exerted minimal antiproliferative effects, DMSO inhibited proliferation in a dose-dependent manner, and the combination of rapamycin and DMSO reduced the number of viable cells significantly more than either agent alone. FACS analysis of propidium iodide-labeled cells revealed a synergistic effect of rapamycin and DMSO on cell cycle arrest in G0/G1 phase. In NB4 cells, rapamycin had no statistically significant effects on DMSO-mediated increase in the expression of CD11b, but increased apoptosis. Conclusion: Rapamycin potentiates growth- inhibitory effects of DMSO in the established leukemia lines. These results suggest that mTOR inhibitors may have beneficial effects in combination with differentiation agents in therapy of AML.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti



POVEZANOST RADA


Projekt / tema
108-1081347-0173 - Funkcija fosfoinozitol 3-kinaze C2 beta u staničnim jezgrama (Hrvoje Banfić, )
108-1081347-1448 - Uloga PLC i Akt u staničnom ciklusu i diferencijaciji leukemija (Dora Višnjić, )

Ustanove
Medicinski fakultet, Zagreb

Citiraj ovu publikaciju

Lalić, Hrvoje; Lukinović-Škudar, Vesna; Banfić, Hrvoje; Višnjić, Dora
Rapamycin enhances dimethyl sulfoxide-mediated growth arrest in human myelogenous leukemia cells // The Annual Symposium of the Croatian Physiological Society with International Participation - Abstract Book
Zagreb: University of Zagreb School of Medicine, 2012. (predavanje, međunarodna recenzija, sažetak, znanstveni)
Lalić, H., Lukinović-Škudar, V., Banfić, H. & Višnjić, D. (2012) Rapamycin enhances dimethyl sulfoxide-mediated growth arrest in human myelogenous leukemia cells. U: The Annual Symposium of the Croatian Physiological Society with International Participation - Abstract Book.
@article{article, year = {2012}, pages = {17}, keywords = {rapamycin, DMSO, acute myeloid leukemia}, title = {Rapamycin enhances dimethyl sulfoxide-mediated growth arrest in human myelogenous leukemia cells}, keyword = {rapamycin, DMSO, acute myeloid leukemia}, publisher = {University of Zagreb School of Medicine}, publisherplace = {Zagreb, Hrvatska} }