Abstract
Purpose
In our previous publication, we have shown that dihydroartemisinin could significantly inhibit the growth of CML K562 cells by its anti-proliferative and inducing apoptotic effects. Given the pivotal effect of Bcr/Abl tyrosine kinase and its downstream signal factors on CML cell proliferation and survival, we extend our study to investigate the effect of DHA on Bcr/Abl and related signal factors to further illuminate the possible mechanisms of the effect of DHA on CML cells.
Methods
The expression of Bcr/Abl was analyzed with PCR and Western blotting methods at both mRNA and protein levels. Measurement of protein expression and tyrosine phosphorylation activity of Bcr/Abl, AKT, ERK1/2, NF-κB and cytochrome c were performed with Western blotting and immunoprecipitation methods. Using the activity kits analyzed the activity of caspase 9 and caspase 3.
Results
The treatment with DHA results in a significant suppression on Bcr/Abl expression and leads to a concentration-dependent reduction on the Bcr/Abl tyrosine activity. Moreover, it also results in a strong influence on the downstream signal factors of Bcr/Abl, which includes inhibition of tyrosine kinase activity of AKT and ERK1/2, suppression of NF-κB protein expression, promotion of the cytochrome c release and the consequential activation of caspase 3/9 in CML K562 cells.
Conclusions
Together with our previous report, our data show that the growth inhibitory effect of DHA on CML cells might be due to the influence on Bcr/Abl expression and its downstream signal factors. DHA might be a potential novel anti-CML drug candidate and worthy of further study.
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Acknowledgments
This work was supported by the Medical Scientific Research Foundation of Zhejiang Province (No. 2008B072) and the project from Administration of Traditional Chinese Medicine of Zhejiang Province, China (No. 2010ZA051).
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Lee, J., Zhang, G., Wu, X. et al. Growth inhibitory effect of dihydroartemisinin on Bcr/Abl+ chronic myeloid leukemia K562 cells involve AKT, ERK and NF-κB modulation. J Cancer Res Clin Oncol 138, 2095–2102 (2012). https://doi.org/10.1007/s00432-012-1292-1
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DOI: https://doi.org/10.1007/s00432-012-1292-1