Synergism between carnosic acid and arsenic trioxide on induction of acute myeloid leukemia cell apoptosis is associated with modulation of PTEN/Akt signaling pathway / 中国结合医学杂志
Chinese journal of integrative medicine
;
(12): 934-941, 2012.
Artigo
em Inglês
| WPRIM
| ID: wpr-293323
ABSTRACT
<p><b>OBJECTIVE</b>To investigate the synergistic effects of carnosic acid (CA) with arsenic trioxide (As₂O₃) on proliferation and apoptosis in HL-60 human myeloid leukemia cells, and the major cellular signaling pathway involved in these effects.</p><p><b>METHODS</b>HL-60 cellular proliferation was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) analysis. Cell cycle distribution and apoptosis were monitored by flow cytometry. The activation of casepase-9, Bcl-2-associated agonist of cell death (BAD), p-BAD, p27, phosphatase and tensin homolog deleted on chromosome ten (PTEN), Akt, p-Akt was assessed by Western blot analysis. The expression of PTEN mRNA was tested by reverse transcription polymerase chain reaction (RT-PCR) analysis.</p><p><b>RESULTS</b>CA reduced HL-60 cell viability in a dose- and time-dependent manner, and induced G1 arrest and apoptosis. Moreover, CA upregulated PTEN expression, blocked the Akt signaling pathway, subsequently inhibited phosphorylation of BAD, reactivated caspase-9, and elevated levels of p27. CA also augmented these effects of As₂O₃.</p><p><b>CONCLUSION</b>CA might be a novel candidate of the combination therapy for leukemia treatment; these effects were apparently associated with the modulation of PTEN/Akt signaling pathway.</p>
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Assunto principal:
Óxidos
/
Patologia
/
Farmacologia
/
Arsenicais
/
Extratos Vegetais
/
Sequência de Bases
/
Leucemia Mieloide Aguda
/
Transdução de Sinais
/
Ciclo Celular
/
Western Blotting
Limite:
Humanos
Idioma:
Inglês
Revista:
Chinese journal of integrative medicine
Ano de publicação:
2012
Tipo de documento:
Artigo
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