Skip to main content
SpringerLink
Log in

Effects of pargyline on cellular proliferation in human breast cancer cells

  • Original Paper
  • Published:
Molecular & Cellular Toxicology Aims and scope Submit manuscript

Abstract

Monoamine oxidase (MAO) inhibitors have been tested for the purpose of treating many types of cancers including breast cancer. Pargyline, an MAO inhibitor, prevents the activity of lysine-specific demethylase 1 (LSD1), which is excessively expressed in breast cancer. The purpose of this study is to investigate the effect of pargyline on cellular proliferation in human breast ductal carcinoma (T47D) cells. After exposing T47D cells to pargyline, we examined cell proliferation, cell cycle, apoptosis, and the expression levels of apoptosis-related proteins and LSD1. The proliferation of cells exposed to pargyline decreased in a dose- and time-dependent manner. The treatment of 2 mM pargyline exhibited an increase of the cell proportion at the G1 phase, while the major decrease of the cell proportion was at the S phase compared to the controls. In addition, pargyline induced an increase in the cleaved PARP expression. However, we did not find a change in the LSD1 expression in the cells exposed to pargyline. Based on our results, it is believed that pargyline has pharmaceutical potential as an anticancer drug for the treatment of human breast cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Mincey, B. A. & Perez, E. A. Advances in screening, diagnosis, and treatment of breast cancer. Mayo Clin Proc 79:810–816 (2004).

    PubMed  Google Scholar 

  2. Dewis, R. & Gribbin, J. Breast cancer: diagnosis and treatment. National Collaborating Centre for Cancer http://www.ncbi.nlm.nih.gov/books/NBK1907/ (2009).

  3. Park, S. K., Kim, Y., Kang, D., Jung, E. J. & Yoo, K. Y. Risk factors and control strategies for the rapidly rising rate of breast cancer in Korea. J Breast Cancer 14:79–87 (2011).

    Article  PubMed  Google Scholar 

  4. Jemal, A. et al. Global cancer statistics. CA Cancer J Clin 61:69–90 (2011).

    Article  PubMed  Google Scholar 

  5. McCloskey, D. E., Casero, R. A., Jr., Woster, P. M. & Davidson, N. E. Induction of programmed cell death in human breast cancer cells by an unsymmetrically alkylated polyamine analogue. Cancer Res 55:3233–3236 (1995).

    PubMed  CAS  Google Scholar 

  6. Huang, Y. et al. A novel polyamine analog inhibits growth and induces apoptosis in human breast cancer cells. Clin Cancer Res 9:2769–2777 (2003).

    PubMed  CAS  Google Scholar 

  7. Zhang, L. & Webster, T. J. Poly-lactic-glycolic-acid surface nanotopographies selectively decrease breast adenocarcinoma cell functions. Nanotechnology 23:155101 (2012).

    Article  PubMed  Google Scholar 

  8. Mertens-Talcott, S. U. et al. Betulinic acid decreases ER-negative breast cancer cell growth in vitro and in vivo: Role of Sp transcription factors and microRNA-27a:ZBTB10. Mol Carcinog DOI: 10. 1002/mc.21893 (2012).

  9. Zhang, X. et al. Effects of the combination of RAD001 and docetaxel on breast cancer stem cells. Eur J Cancer http://dx.doi.org/10.1016/j.ejca.2012.02.053 (2012).

  10. Cortez, V. et al. Targeting the PELP1-KDM1 axis as a potential therapeutic strategy for breast cancer. Breast Cancer Res 14:R108 (2012).

    Article  PubMed  CAS  Google Scholar 

  11. Widschwendter, M. & Jones, P. A. DNA methylation and breast carcinogenesis. Oncogene 21:5462–5482 (2002).

    Article  PubMed  CAS  Google Scholar 

  12. Lim, S. et al. Lysine-specific demethylase 1 (LSD1) is highly expressed in ER-negative breast cancers and a biomarker predicting aggressive biology. Carcinogenesis 31:512–520 (2010).

    Article  PubMed  CAS  Google Scholar 

  13. Schulte, J. H. et al. Lysine-specific demethylase 1 is strongly expressed in poorly differentiated neuroblastoma: implications for therapy. Cancer Res 69:2065–2071 (2009).

    Article  PubMed  CAS  Google Scholar 

  14. Shi, Y. et al. Histone demethylation mediated by the nuclear amine oxidase homolog LSD1. Cell 119:941–953 (2004).

    Article  PubMed  CAS  Google Scholar 

  15. Humphrey, G. W. et al. Stable histone deacetylase complexes distinguished by the presence of SANT domain proteins CoREST/kiaa0071 and Mta-L1. J Biol Chem 276:6817–6824 (2001).

    Article  PubMed  CAS  Google Scholar 

  16. Bannister, A. J., Schneider, R. & Kouzarides, T. Histone methylation: dynamic or static? Cell 109:801–806 (2002).

    Article  PubMed  CAS  Google Scholar 

  17. Schmidt, D. M. & McCafferty, D. G. trans-2-Phenylcyclopropylamine is a mechanism-based inactivator of the histone demethylase LSD1. Biochemistry 46: 4408–4416 (2007).

    Article  PubMed  CAS  Google Scholar 

  18. Mimasu, S. et al. Structurally designed trans-2-phenylcyclopropylamine derivatives potently inhibit histone demethylase LSD1/KDM1. Biochemistry 49:6494–6503 (2010).

    Article  PubMed  CAS  Google Scholar 

  19. Huang, Y., Vasilatos, S. N., Boric, L., Shaw, P. G. & Davidson, N. E. Inhibitors of histone demethylation and histone deacetylation cooperate in regulating gene expression and inhibiting growth in human breast cancer cells. Breast Cancer Res Treat 131:777–789 (2012).

    Article  PubMed  CAS  Google Scholar 

  20. Zhu, Q. et al. Polyamine analogs modulate gene expression by inhibiting lysine-specific demethylase 1 (LSD1) and altering chromatin structure in human breast cancer cells. Amino acids 42:887–898 (2012).

    Article  PubMed  CAS  Google Scholar 

  21. Huang, Y. et al. Novel oligoamine analogues inhibit lysine-specific demethylase 1 and induce reexpression of epigenetically silenced genes. Clin Cancer Res 15: 7217–7228 (2009).

    Article  PubMed  CAS  Google Scholar 

  22. Casero, R. A., Jr. & Woster, P. M. Recent advances in the development of polyamine analogues as antitumor agents. J Med Chem 52:4551–4573 (2009).

    Article  PubMed  CAS  Google Scholar 

  23. Sharma, S. K. et al. (Bis)urea and (bis)thiourea inhibitors of lysine-specific demethylase 1 as epigenetic modulators. J Med Chem 53:5197–5212 (2010).

    Article  PubMed  CAS  Google Scholar 

  24. Kuribayashi, K., Mayes, P. A. & El-Deiry, W. S. What are caspases 3 and 7 doing upstream of the mitochondria? Cancer Biol Ther 5:763–765 (2006).

    Article  PubMed  CAS  Google Scholar 

  25. Chiu, S. C. et al. Poly (ADP-ribose) polymerase plays an important role in intermittent hypoxia-induced cell death in rat cerebellar granule cells. J Biomed Sci 19:29 (2012).

    Article  PubMed  CAS  Google Scholar 

  26. Huang, Y., Vasilatos, S. N., Boric, L., Shaw, P. G. & Davidson, N. E. Inhibitors of histone demethylation and histone deacetylation cooperate in regulating gene expression and inhibiting growth in human breast cancer cells. Breast Cancer Res Treat 131:777–789 (2012).

    Article  PubMed  CAS  Google Scholar 

  27. Flamand, V., Zhao, H. & Peehl, D. M. Targeting monoamine oxidase A in advanced prostate cancer. J Cancer Res Clin Oncol 136:1761–1771 (2010).

    Article  PubMed  CAS  Google Scholar 

  28. Singh, M. M. et al. Inhibition of LSD1 sensitizes glioblastoma cells to histone deacetylase inhibitors. Neuro Oncol 13:894–903 (2011).

    Article  PubMed  CAS  Google Scholar 

  29. Chuang, J. Y., Chang, W. C. & Hung, J. J. Hydrogen peroxide induces Sp1 methylation and thereby suppresses cyclin B1 via recruitment of Suv39H1 and HDAC1 in cancer cells. Free Radic Biol Med 51:2309–2318 (2011).

    Article  PubMed  CAS  Google Scholar 

  30. Cao, M. R. et al. Harmine induces apoptosis in HepG2 cells via mitochondrial signaling pathway. Hepatobiliary Pancreat Dis Int 10:599–604 (2011).

    Article  PubMed  CAS  Google Scholar 

  31. Cakir, E. et al. Prognostic significance of micropapillary pattern in lung adenocarcinoma and expression of apoptosis-related markers: caspase-3, bcl-2, and p53. APMIS 119:574–580 (2011).

    Article  PubMed  Google Scholar 

  32. Oliver, F. J. et al. Importance of poly (ADP-ribose) polymerase and its cleavage in apoptosis. Lesson from an uncleavable mutant. J Biol Chem 273:33533–33539 (1998).

    Article  PubMed  CAS  Google Scholar 

  33. Kunduzova, O. R. et al. Regulation of JNK/ERK activation, cell apoptosis, and tissue regeneration by monoamine oxidases after renal ischemia-reperfusion. FASEB J 16:1129–1131 (2002).

    PubMed  CAS  Google Scholar 

  34. Chaaya, R. et al. Pargyline reduces renal damage associated with ischaemia-reperfusion and cyclosporin. Nephrol Dial Transplant 26:489–498 (2011).

    Article  PubMed  CAS  Google Scholar 

  35. Jung, K. H. et al. Early response in macrophages by exposure to a low concentration of anthrax lethal toxin. Mol Cell Toxicol 7:45–52 (2011).

    Article  CAS  Google Scholar 

  36. Choi, M. R. et al. Fluoxetine Up-Regulates Bcl-xL Expression in Rat C6 Glioma Cells. Psychiatry Investig 8:161–168 (2011).

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Molecular and Life Sciences, Hanyang University, Ansan, Korea

    Hyung Tae Lee, Kyoung Hwa Jung, Se Kye Kim, Mi Ran Choi & Young Gyu Chai

Authors
  1. Hyung Tae Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kyoung Hwa Jung
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Se Kye Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mi Ran Choi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Young Gyu Chai
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Mi Ran Choi or Young Gyu Chai.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lee, H.T., Jung, K.H., Kim, S.K. et al. Effects of pargyline on cellular proliferation in human breast cancer cells. Mol. Cell. Toxicol. 8, 393–399 (2012). https://doi.org/10.1007/s13273-012-0048-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13273-012-0048-y

Keywords

Search

Navigation