Synergism between carnosic acid and arsenic trioxide on induction of acute myeloid leukemia cell apoptosis is associated with modulation of PTEN/Akt signaling pathway.
- Author:
Ran WANG
1
;
Wei-hong CONG
;
Gang GUO
;
Xiang-xin LI
;
Xue-liang CHEN
;
Xiao-ning YU
;
Hao LI
Author Information
- Publication Type:Journal Article
- MeSH: Apoptosis; drug effects; Arsenicals; pharmacology; Base Sequence; Blotting, Western; Cell Cycle; drug effects; DNA Primers; Diterpenes, Abietane; pharmacology; Drug Synergism; HL-60 Cells; Humans; Leukemia, Myeloid, Acute; metabolism; pathology; Oxides; pharmacology; PTEN Phosphohydrolase; metabolism; Plant Extracts; pharmacology; Proto-Oncogene Proteins c-akt; metabolism; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction; drug effects
- From: Chinese journal of integrative medicine 2012;18(12):934-941
- CountryChina
- Language:English
-
Abstract:
OBJECTIVETo 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.
METHODSHL-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.
RESULTSCA 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.
CONCLUSIONCA 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.