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The mechanism of synergistic effects of arsenic trioxide and rapamycin in acute myeloid leukemia cell lines lacking typical t(15 ; 17) translocation


Dembitz, Vilma; Lalić, Hrvoje; Ostojić, Alen; Vrhovac, Radovan; Banfić, Hrvoje; Višnjić, Dora
The mechanism of synergistic effects of arsenic trioxide and rapamycin in acute myeloid leukemia cell lines lacking typical t(15 ; 17) translocation // International journal of hematology, 102 (2015), 1; 12-24 doi:10.1007/s12185-015-1776-2 (međunarodna recenzija, članak, znanstveni)


Naslov
The mechanism of synergistic effects of arsenic trioxide and rapamycin in acute myeloid leukemia cell lines lacking typical t(15 ; 17) translocation

Autori
Dembitz, Vilma ; Lalić, Hrvoje ; Ostojić, Alen ; Vrhovac, Radovan ; Banfić, Hrvoje ; Višnjić, Dora

Izvornik
International journal of hematology (0925-5710) 102 (2015), 1; 12-24

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
Arsenic trioxide; Rapamycin; U937; HL-60; CD64

Sažetak
Arsenic trioxide (ATO) has potent clinical activity in the treatment of patients with acute promyelocytic leukemia (APL), but is much less efficacious in acute myeloid leukemia (AML) lacking t(15 ; 17) translocation. Recent studies have indicated that the addition of mammalian target of rapamycin (mTOR) inhibitors may increase the sensitivity of malignant cells to ATO. The aim of the present study was to test for possible synergistic effects of ATO and rapamycin at therapeutically achievable doses in non-APL AML cells. In HL-60 and U937 cell lines, the inhibitory effects of low concentrations of ATO and rapamycin were synergistic and more pronounced in U937 cells. The combination of drugs increased apoptosis in HL-60 cells and increased the percentage of cells in G0/G1 phase in both cell lines. In U937 cells, rapamycin alone increased the activity of mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) and the addition of ATO decreased the level of phosphorylated ERK, Ser473 phosphorylated Akt and anti-apoptotic Mcl-1 protein. Primary AML cells show high sensitivity to growth-inhibitory effects of rapamycin alone or in combination with ATO. The results of the present study reveal the mechanism of the synergistic effects of two drugs at therapeutically achievable doses in non-APL AML cells.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti



POVEZANOST RADA


Projekt / tema
108-0000000-3455 - Dijagnostika i terapija infekcija kod imunokompromitiranih bolesnika (Radovan Vrhovac, )
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,
Klinički bolnički centar Zagreb

Profili:

Avatar Url Hrvoje Banfić (autor)

Avatar Url Dora Višnjić (autor)

Avatar Url Radovan Vrhovac (autor)

Avatar Url Hrvoje Lalić (autor)

Avatar Url Vilma Dembitz (autor)

Citiraj ovu publikaciju

Dembitz, Vilma; Lalić, Hrvoje; Ostojić, Alen; Vrhovac, Radovan; Banfić, Hrvoje; Višnjić, Dora
The mechanism of synergistic effects of arsenic trioxide and rapamycin in acute myeloid leukemia cell lines lacking typical t(15 ; 17) translocation // International journal of hematology, 102 (2015), 1; 12-24 doi:10.1007/s12185-015-1776-2 (međunarodna recenzija, članak, znanstveni)
Dembitz, V., Lalić, H., Ostojić, A., Vrhovac, R., Banfić, H. & Višnjić, D. (2015) The mechanism of synergistic effects of arsenic trioxide and rapamycin in acute myeloid leukemia cell lines lacking typical t(15 ; 17) translocation. International journal of hematology, 102 (1), 12-24 doi:10.1007/s12185-015-1776-2.
@article{article, year = {2015}, pages = {12-24}, DOI = {10.1007/s12185-015-1776-2}, keywords = {Arsenic trioxide, Rapamycin, U937, HL-60, CD64}, journal = {International journal of hematology}, doi = {10.1007/s12185-015-1776-2}, volume = {102}, number = {1}, issn = {0925-5710}, title = {The mechanism of synergistic effects of arsenic trioxide and rapamycin in acute myeloid leukemia cell lines lacking typical t(15 ; 17) translocation}, keyword = {Arsenic trioxide, Rapamycin, U937, HL-60, CD64} }

Časopis indeksira:


  • Current Contents Connect (CCC)
  • Web of Science Core Collection (WoSCC)
    • Science Citation Index Expanded (SCI-EXP)
    • SCI-EXP, SSCI i/ili A&HCI
  • Scopus
  • MEDLINE


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