Synergism between Carnosic Acid and Arsenic Trioxide on Induction of Acute Myeloid Leukemia Cell Apoptosis Is Associated with Modulation of PTEN/Akt Signaling Pathway

• Published in: Chinese journal of integrative medicine 2012-12, Vol.18 (12), p.934-941
• Main Author: 王冉 丛伟红 郭刚 李湘新 陈学良 于晓宁 李颢
• Format: Article
• Language: English
• Subjects: Akt; Apoptosis - drug effects; Arsenicals - pharmacology; Base Sequence; Blotting, Western; Cell Cycle - drug effects; Diterpenes, Abietane - pharmacology; DNA Primers; Drug Synergism; HL-60 Cells; Humans; Leukemia, Myeloid, Acute - metabolism; Leukemia, Myeloid, Acute - pathology; Medicine; Medicine & Public Health; Original Article; Oxides - pharmacology; Plant Extracts - pharmacology; Proto-Oncogene Proteins c-akt - metabolism; PTEN Phosphohydrolase - metabolism; PTEN基因; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction - drug effects; 三氧化二砷; 信号通路; 协同作用; 白血病细胞; 细胞凋亡; 诱导
• ISSN: 1672-0415; 1993-0402
• DOI: 10.1007/s11655-012-1297-z

Objective： To investigate the synergistic effects of carnosic acid （CA） with arsenic trioxide （As203） on proliferation and apoptosis in HL-60 human myeloid leukemia cells, and the major cellular signaling pathway involved in these effects. Methods： HL-60 cellular proliferation was measured by 3-（4,5-dimethylthiazol-2-yl）- 2,5-diphenyltetrazolium bromide （MTF） 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. Results： 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 As203. Conclusion： 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.