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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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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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Authors and Affiliations

  1. Department of Hematology, Qilu Hospital of Shandong University, Jinan, 250012, China

    Ran Wang  (王 冉), Xiang-xin Li  (李湘新), Xue-liang Chen  (陈学良) & Hao Li  (李 颢)

  2. Research Center, Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing, 100091, China

    Wei-hong Cong  (丛伟红)

  3. Department of Scientific Research, Qilu Hospital of Shandong University, Jinan, 250012, China

    Gang Guo  (郭 刚)

  4. Department of Health Care, Qilu Hospital of Shandong University, Jinan, 250012, China

    Xiao-ning Yu  (于晓宁)

Authors
  1. Ran Wang  (王 冉)
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  2. Wei-hong Cong  (丛伟红)
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  3. Gang Guo  (郭 刚)
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  4. Xiang-xin Li  (李湘新)
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  5. Xue-liang Chen  (陈学良)
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  6. Xiao-ning Yu  (于晓宁)
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  7. Hao Li  (李 颢)
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Corresponding author

Correspondence to Hao Li  (李 颢).

Additional information

Supported by the National Natural Science Foundation of China (No. 81102710)

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Wang, R., Cong, Wh., Guo, G. et al. Synergism between carnosic acid and arsenic trioxide on induction of acute myeloid leukemia cell apoptosis is associated with modulation of PTEN/Akt signaling pathway. Chin. J. Integr. Med. 18, 934–941 (2012). https://doi.org/10.1007/s11655-012-1297-z

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  • DOI: https://doi.org/10.1007/s11655-012-1297-z

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