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.
Article
in En
| WPRIM
| ID: wpr-293323
Responsible library:
WPRO
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>
Full text:
1
Database:
WPRIM
Main subject:
Oxides
/
Pathology
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Pharmacology
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Arsenicals
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Plant Extracts
/
Base Sequence
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Leukemia, Myeloid, Acute
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Signal Transduction
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Cell Cycle
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Blotting, Western
Limits:
Humans
Language:
En
Journal:
Chinese journal of integrative medicine
Year:
2012
Document type:
Article