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

【摘要】 <正>Objective: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.Methods: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.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 As₂O₃.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.更多还原

【Abstract】 Objective: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.Methods: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.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 As₂O₃.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.更多还原