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Article

L‑Deprenyl exerts cytotoxicity towards acute myeloid leukemia through inhibition of mitochondrial respiration

  • Authors:
    • Ilhwan Ryu
    • Min Jeong Ryu
    • Jeongsu Han
    • Soo Jeong Kim
    • Min Joung Lee
    • Xianshu Ju
    • Byeong Hyeon Yoo
    • Yu Lim Lee
    • Yunseon Jang
    • Ik‑Chan Song
    • Woosuk Chung
    • Eungseok Oh
    • Jun Young Heo
    • Gi Ryang Kweon
  • View Affiliations / Copyright

    Affiliations: Department of Biochemistry, Chungnam National University School of Medicine, Daejeon 35015, Republic of Korea, Department of Medical Science, Chungnam National University School of Medicine, Daejeon 35015, Republic of Korea, Department of Internal Medicine, Chungnam National University Hospital, Daejeon 35015, Republic of Korea, Department of Neurology, Chungnam National University Hospital, Daejeon 35015, Republic of Korea
  • Pages: 3869-3878
    |
    Published online on: October 1, 2018
       https://doi.org/10.3892/or.2018.6753
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Abstract

The identification of large numbers of genetic mutations in immature myeloid cells has made it difficult to identify specific targets for acute myeloid leukemia (AML) therapy. Although current pharmacological targets for controlling cancer are focused on identifying genetic mutations, it is hard to develop the specific drugs to achieve complete remission due to complex and variable genetic mutations. To overcome the failure of the genetic mutation theory, the present study targeted mitochondrial metabolism as a strategy for inducing anti‑leukemic activity, based on evidence that AML cells have an abnormally high amount of mitochondria and that somatic mutations can alter metabolic flux in cancer. It was found that L‑deprenyl, which is clinically available for the treatment of Parkinson's disease, exerts anti‑mitochondria activity in KG‑1α cells, as assessed by detection of oxygen consumption rate (OCR) and extracellular acidification (ECAR) using XF analyzer, respectively. Using a luciferase assay for detecting adenosine triphosphate (ATP) content, it was found that suppression of mitochondrial activity led to ATP depletion and was associated with potent cytotoxic activity. L‑deprenyl is known to target monoamine oxidase‑B (MAO‑B) on the outer membrane of mitochondria, therefore, the activity of MAO‑A and ‑B was measured based on the fluorometric detection of H2O2 produced by the enzyme reaction. Notably, MAO‑A and -B activity was low in AML cells and the present findings suggested that the anticancer effect of L‑deprenyl was independent of MAO‑B. Change of mitochondrial respiration‑ and glycolysis‑related gene expression levels were measured by reverse transcription‑quantitative polymerase chain reaction. Consistent with the aforementioned results, treatment with L‑deprenyl reduced the mRNA level of mitochondrial respiration‑ and glycolysis‑related genes. Collectively, the present results identify L‑deprenyl as a novel candidate for the treatment of AML through inhibition of mitochondrial respiration.
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Copy and paste a formatted citation
Spandidos Publications style
Ryu I, Ryu MJ, Han J, Kim SJ, Lee MJ, Ju X, Yoo BH, Lee YL, Jang Y, Song IC, Song IC, et al: L‑Deprenyl exerts cytotoxicity towards acute myeloid leukemia through inhibition of mitochondrial respiration. Oncol Rep 40: 3869-3878, 2018.
APA
Ryu, I., Ryu, M.J., Han, J., Kim, S.J., Lee, M.J., Ju, X. ... Kweon, G.R. (2018). L‑Deprenyl exerts cytotoxicity towards acute myeloid leukemia through inhibition of mitochondrial respiration. Oncology Reports, 40, 3869-3878. https://doi.org/10.3892/or.2018.6753
MLA
Ryu, I., Ryu, M. J., Han, J., Kim, S. J., Lee, M. J., Ju, X., Yoo, B. H., Lee, Y. L., Jang, Y., Song, I., Chung, W., Oh, E., Heo, J. Y., Kweon, G. R."L‑Deprenyl exerts cytotoxicity towards acute myeloid leukemia through inhibition of mitochondrial respiration". Oncology Reports 40.6 (2018): 3869-3878.
Chicago
Ryu, I., Ryu, M. J., Han, J., Kim, S. J., Lee, M. J., Ju, X., Yoo, B. H., Lee, Y. L., Jang, Y., Song, I., Chung, W., Oh, E., Heo, J. Y., Kweon, G. R."L‑Deprenyl exerts cytotoxicity towards acute myeloid leukemia through inhibition of mitochondrial respiration". Oncology Reports 40, no. 6 (2018): 3869-3878. https://doi.org/10.3892/or.2018.6753
Copy and paste a formatted citation
x
Spandidos Publications style
Ryu I, Ryu MJ, Han J, Kim SJ, Lee MJ, Ju X, Yoo BH, Lee YL, Jang Y, Song IC, Song IC, et al: L‑Deprenyl exerts cytotoxicity towards acute myeloid leukemia through inhibition of mitochondrial respiration. Oncol Rep 40: 3869-3878, 2018.
APA
Ryu, I., Ryu, M.J., Han, J., Kim, S.J., Lee, M.J., Ju, X. ... Kweon, G.R. (2018). L‑Deprenyl exerts cytotoxicity towards acute myeloid leukemia through inhibition of mitochondrial respiration. Oncology Reports, 40, 3869-3878. https://doi.org/10.3892/or.2018.6753
MLA
Ryu, I., Ryu, M. J., Han, J., Kim, S. J., Lee, M. J., Ju, X., Yoo, B. H., Lee, Y. L., Jang, Y., Song, I., Chung, W., Oh, E., Heo, J. Y., Kweon, G. R."L‑Deprenyl exerts cytotoxicity towards acute myeloid leukemia through inhibition of mitochondrial respiration". Oncology Reports 40.6 (2018): 3869-3878.
Chicago
Ryu, I., Ryu, M. J., Han, J., Kim, S. J., Lee, M. J., Ju, X., Yoo, B. H., Lee, Y. L., Jang, Y., Song, I., Chung, W., Oh, E., Heo, J. Y., Kweon, G. R."L‑Deprenyl exerts cytotoxicity towards acute myeloid leukemia through inhibition of mitochondrial respiration". Oncology Reports 40, no. 6 (2018): 3869-3878. https://doi.org/10.3892/or.2018.6753
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