Effects of the monoamine oxidase inhibitors pargyline and tranylcypromine on cellular proliferation in human prostate cancer cells

Lee,Hyung   Tae; Choi,Mi  Ran; Doh,Mi   Sook; Jung,Kyoung   Hwa; Chai,Young  Gyu

doi:10.3892/or.2013.2635

Effects of the monoamine oxidase inhibitors pargyline and tranylcypromine on cellular proliferation in human prostate cancer cells

Authors:
- Hyung Tae Lee
- Mi Ran Choi
- Mi Sook Doh
- Kyoung Hwa Jung
- Young Gyu Chai
View Affiliations

Affiliations: Department of Molecular and Life Sciences, Hanyang University, Ansan 426-791, Republic of Korea
Published online on: July 24, 2013 https://doi.org/10.3892/or.2013.2635
Pages: 1587-1592
Copyright: © Lee et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Chemotherapy is one of the therapeutic strategies that has been used for the inhibition of cancer cell proliferation in several types of cancer, including prostate cancer. Although monoamine oxidase (MAO) inhibitors, phytoestrogen and antioxidants used in chemotherapy have been systematically studied, their effects on cancer cell growth remain to be fully understood. The purpose of this study was to investigate the effects of the MAO inhibitors, pargyline and tranylcypromine on cell survival in human prostate carcinoma (LNCaP-LN3) cells. After treating LNCaP-LN3 cells with pargyline or tranylcypromine, we examined cell proliferation, cell cycle pattern, apoptosis and the expression levels of apoptosis-related genes. The proliferation of cells exposed to pargyline decreased in a dose- and time-dependent manner, while tranylcypromine-treated cells showed the opposite results. Treatment with pargyline significantly induced cell cycle arrest at the G1 phase compared to the control and tranylcypromine-treated cells. In addition, pargyline induced an increase in the cell death rate by promoting apoptosis; however, tranylcypromine had no effect on LNCaP-LN3 cells. Based on our results, we suggest that pargyline is more powerful than tranylcypromine for the treatment of human prostate cancer.

View Figures

View References

1	Siegel R, Ward E, Brawley O and Jemal A: Cancer statistics, 2011: the impact of eliminating socioeconomic and racial disparities on premature cancer deaths. CA Cancer J Clin. 61:212–236. 2011. View Article : Google Scholar : PubMed/NCBI
2	Dunn MW and Kazer MW: Prostate cancer overview. Semin Oncol Nurs. 27:241–250. 2011. View Article : Google Scholar
3	McCloskey DE, Casero RA Jr, Woster PM and Davidson NE: Induction of programmed cell death in human breast cancer cells by an unsymmetrically alkylated polyamine analogue. Cancer Res. 55:3233–3236. 1995.PubMed/NCBI
4	Huang Y, Hager ER, Phillips DL, et al: A novel polyamine analog inhibits growth and induces apoptosis in human breast cancer cells. Clin Cancer Res. 9:2769–2777. 2003.PubMed/NCBI
5	Zhang L and Webster TJ: Poly-lactic-glycolic-acid surface nanotopographies selectively decrease breast adenocarcinoma cell functions. Nanotechnology. 23:1551012012. View Article : Google Scholar : PubMed/NCBI
6	Mertens-Talcott SU, Noratto GD, Li X, Angel-Morales G, Bertoldi MC and Safe S: 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. Mar 7–2012.(Epub ahead of print). View Article : Google Scholar
7	Zhang X, Zhang S, Liu Y, et al: Effects of the combination of RAD001 and docetaxel on breast cancer stem cells. Eur J Cancer. 48:1581–1592. 2012. View Article : Google Scholar : PubMed/NCBI
8	Thapa D and Ghosh R: Antioxidants for prostate cancer chemoprevention: challenges and opportunities. Biochem Pharmacol. 83:1319–1330. 2012. View Article : Google Scholar : PubMed/NCBI
9	Kumar R, Verma V, Jain A, Jain RK, Maikhuri JP and Gupta G: Synergistic chemoprotective mechanisms of dietary phytoestrogens in a select combination against prostate cancer. J Nutr Biochem. 22:723–731. 2011. View Article : Google Scholar : PubMed/NCBI
10	Huang CH, Guh JH, Chen GS, Lu PH and Chern JW: Anticancer activity of a cyclooxygenase inhibitor, CX9051, in human prostate cancer cells: the roles of NF-κB and crosstalk between the extrinsic and intrinsic apoptotic pathways. Naunyn Schmiedebergs Arch Pharmacol. 382:159–169. 2010.PubMed/NCBI
11	Lim S, Janzer A, Becker A, 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. View Article : Google Scholar : PubMed/NCBI
12	Schmidt DM and McCafferty DG: trans-2-Phenylcyclopropylamine is a mechanism-based inactivator of the histone demethylase LSD1. Biochemistry. 46:4408–4416. 2007. View Article : Google Scholar : PubMed/NCBI
13	Cortez V, Mann M, Tekmal S, et al: Targeting the PELP1-KDM1 axis as a potential therapeutic strategy for breast cancer. Breast Cancer Res. 14:R1082012. View Article : Google Scholar : PubMed/NCBI
14	Flamand V, Zhao H and Peehl DM: Targeting monoamine oxidase A in advanced prostate cancer. J Cancer Res Clin Oncol. 136:1761–1771. 2010. View Article : Google Scholar : PubMed/NCBI
15	Schulte JH, Lim S, Schramm A, et al: Lysine-specific demethylase 1 is strongly expressed in poorly differentiated neuroblastoma: implications for therapy. Cancer Res. 69:2065–2071. 2009. View Article : Google Scholar
16	Lee HT, Jung KH, Kim SK, Choi MR and Chai YG: Effects of pargyline on cellular proliferation in human breast cancer cells. Mol Cell Toxicol. 8:393–399. 2012. View Article : Google Scholar
17	Lee HT, Kim SK, Choi MR, Park JH, Jung KH and Chai YG: Effects of the activated mitogen-activated protein kinase pathway via the c-ros receptor tyrosine kinase on the T47D breast cancer cell line following alcohol exposure. Oncol Rep. 29:868–874. 2013.PubMed/NCBI
18	Baik SY, Jung KH, Choi MR, et al: Fluoxetine-induced up-regulation of 14-3-3zeta and tryptophan hydroxylase levels in RBL-2H3 cells. Neurosci Lett. 374:53–57. 2005. View Article : Google Scholar : PubMed/NCBI
19	Choi MR, Oh DH, Kim SH, et al: Fluoxetine up-regulates Bcl-xL expression in rat C6 glioma cells. Psychiatry Investig. 8:161–168. 2011. View Article : Google Scholar : PubMed/NCBI
20	Jemal A, Bray F, Center MM, Ferlay J, Ward E and Forman D: Global cancer statistics. CA Cancer J Clin. 61:69–90. 2011. View Article : Google Scholar
21	Pollock JA, Larrea MD, Jasper JS, McDonnell DP and McCafferty DG: Lysine-specific histone demethylase 1 inhibitors control breast cancer proliferation in ERα-dependent and -independent manners. ACS Chem Biol. 7:1221–1231. 2012.PubMed/NCBI
22	Benelkebir H, Hodgkinson C, Duriez PJ, et al: Enantioselective synthesis of tranylcypromine analogues as lysine demethylase (LSD1) inhibitors. Bioorg Med Chem. 19:3709–3716. 2011. View Article : Google Scholar : PubMed/NCBI
23	Kim SJ, Min HY, Lee EJ, et al: Growth inhibition and cell cycle arrest in the G0/G1 by schizandrin, a dibenzocyclooctadiene lignan isolated from Schisandra chinensis, on T47D human breast cancer cells. Phytother Res. 24:193–197. 2010.PubMed/NCBI
24	Chuang JY, Chang WC and Hung JJ: 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. View Article : Google Scholar : PubMed/NCBI
25	Gatta R and Mantovani R: NF-Y substitutes H2A-H2B on active cell-cycle promoters: recruitment of CoREST-KDM1 and fine-tuning of H3 methylations. Nucleic Acids Res. 36:6592–6607. 2008. View Article : Google Scholar
26	Martinou JC and Youle RJ: Mitochondria in apoptosis: Bcl-2 family members and mitochondrial dynamics. Dev Cell. 21:92–101. 2011. View Article : Google Scholar : PubMed/NCBI
27	Rosser CJ, Gaar M and Porvasnik S: Molecular fingerprinting of radiation resistant tumors: can we apprehend and rehabilitate the suspects? BMC Cancer. 9:2252009. View Article : Google Scholar : PubMed/NCBI
28	Lucken-Ardjomande S and Martinou JC: Regulation of Bcl-2 proteins and of the permeability of the outer mitochondrial membrane. CR Biol. 328:616–631. 2005. View Article : Google Scholar : PubMed/NCBI
29	Oda E, Ohki R, Murasawa H, et al: Noxa, a BH3-only member of the Bcl-2 family and candidate mediator of p53-induced apoptosis. Science. 288:1053–1058. 2000. View Article : Google Scholar : PubMed/NCBI
30	Smith AJ, Dai H, Correia C, et al: Noxa/Bcl-2 protein interactions contribute to bortezomib resistance in human lymphoid cells. J Biol Chem. 286:17682–17692. 2011. View Article : Google Scholar : PubMed/NCBI
31	Ploner C, Kofler R and Villunger A: Noxa: at the tip of the balance between life and death. Oncogene. 27(Suppl 1): S84–S92. 2008. View Article : Google Scholar : PubMed/NCBI
32	Shibue T, Takeda K, Oda E, et al: Integral role of Noxa in p53-mediated apoptotic response. Genes Dev. 17:2233–2238. 2003. View Article : Google Scholar : PubMed/NCBI
33	Adams JM and Cory S: The Bcl-2 protein family: arbiters of cell survival. Science. 281:1322–1326. 1998. View Article : Google Scholar : PubMed/NCBI
34	Elmore S: Apoptosis: a review of programmed cell death. Toxicol Pathol. 35:495–516. 2007. View Article : Google Scholar : PubMed/NCBI
35	Malorni W, Giammarioli AM, Matarrese P, et al: Protection against apoptosis by monoamine oxidase A inhibitors. FEBS Lett. 426:155–159. 1998. View Article : Google Scholar : PubMed/NCBI
36	Singh MM, Manton CA, Bhat KP, et al: Inhibition of LSD1 sensitizes glioblastoma cells to histone deacetylase inhibitors. Neuro Oncol. 13:894–903. 2011. View Article : Google Scholar : PubMed/NCBI