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| Synergism between carnosic acid and arsenic trioxide on induction of acute myeloid leukemia cell apoptosis is associated with modulation of PTEN/Akt signaling pathway |
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| Author Name | Affiliation | E-mail | | Ran Wang | Department of Hematology, Qilu Hospital of Shandong University, Jinan, 250012, China | | | Wei-hong Cong | Research Center, Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing, 100091, China | | | Gang Guo | Department of Scientific Research, Qilu Hospital of Shandong University, Jinan, 250012, China | | | Xiang-xin Li | Department of Hematology, Qilu Hospital of Shandong University, Jinan, 250012, China | | | Xue-liang Chen | Department of Hematology, Qilu Hospital of Shandong University, Jinan, 250012, China | | | Xiao-ning Yu | Department of Health Care, Qilu Hospital of Shandong University, Jinan, 250012, China | | | Hao Li | Department of Hematology, Qilu Hospital of Shandong University, Jinan, 250012, China | haoli611@yahoo.com.cn |
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| 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. |
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