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.
OBJECTIVE: To investigate the synergistic effects of carnosic acid (CA) with arsenic trioxide (As₂O₃) on proliferation and apoptosis in HL-60 humanmyeloid 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.
Authors: C Niu; H Yan; T Yu; H P Sun; J X Liu; X S Li; W Wu; F Q Zhang; Y Chen; L Zhou; J M Li; X Y Zeng; R R Yang; M M Yuan; M Y Ren; F Y Gu; Q Cao; B W Gu; X Y Su; G Q Chen; S M Xiong; T D Zhang; S Waxman; Z Y Wang; Z Chen; J Hu; Z X Shen; S J Chen Journal: Blood Date: 1999-11-15 Impact factor: 22.113
Authors: Alberto Valdés; Virginia García-Cañas; Konstantin A Artemenko; Carolina Simó; Jonas Bergquist; Alejandro Cifuentes Journal: Mol Cell Proteomics Date: 2016-11-10 Impact factor: 5.911