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

Cited by 37 publications

(22 citation statements)

References 33 publications

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“…A Korean research team recently published that the MAO inhibitors pargyline and tranylcypromine affected the cell cycle in human prostate carcinoma (LNCAP-LN3) cells and that pargyline was more effective than tranylcypromine (Lee et al, 2013). Efficacy of pargyline to inhibit the growth of breast cancer cells has also been described (Lee et al, 2012).…”

Section: Other Diseasesmentioning

confidence: 99%

Monoamine Oxidase Inhibitors—Revisiting a Therapeutic Principle

Entzeroth¹,

Ratty²

2017

OJD

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Over more than 60 years, monoamine oxidase (MAO) inhibitors are available for therapy of central nervous diseases. Although they have shown to be efficacious specifically in the treatment of major depressive disorders and treatment-resistant depression, they became less a therapeutic choice for the physicians mostly due to severe side effects, such as liver failure and hypertensive crisis associated specifically with the first generation of inhibitors. Nevertheless, this class of drugs is still being used for treatment specifically as more selective and reversible inhibitors became available and will provide clinicians with additional treatment options. The current review revisits monoamine oxidase inhibitors and their potential in the treatment of human diseases, such as anxiety, depression, mood and personality disorders, and pain and introduces current ideas and developments.

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Section: Other Diseasesmentioning

confidence: 99%

Monoamine Oxidase Inhibitors—Revisiting a Therapeutic Principle

Entzeroth¹,

Ratty²

2017

OJD

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“…19 Pargyline, a monoamine oxidase (MAO) inhibitor, effectively inhibits the activity of LSD1. 20,21 Pargyline was used initially in the treatment of hypertension 22 and also represents a promising anti-cancer drug in the field of epigenetic therapy. 23–25 On the basis of these clinical applications, the pharmacokinetics and safety considerations of pargyline have been evaluated, 20,21 which makes its translation and potential application in the field of osteoporosis and MSC-based bone tissue engineering possible and easier.…”

Section: Introductionmentioning

confidence: 99%

Lysine-specific demethylase 1 inhibitor rescues the osteogenic ability of mesenchymal stem cells under osteoporotic conditions by modulating H3K4 methylation

Liu

et al. 2016

Bone Res

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Bone tissue engineering may be hindered by underlying osteoporosis because of a decreased osteogenic ability of autologous seed cells and an unfavorably changed microenvironment in these patients. Epigenetic regulation plays an important role in the developmental origins of osteoporosis; however, few studies have investigated the potential of epigenetic therapy to improve or rescue the osteogenic ability of bone marrow mesenchymal stem cells (BMMSCs) under osteoporotic conditions. Here, we investigated pargyline, an inhibitor of lysine-specific demethylase 1 (LSD1), which mainly catalyzes the demethylation of the di- and mono-methylation of H3K4. We demonstrated that 1.5 mmol·L−1 pargyline was the optimal concentration for the osteogenic differentiation of human BMMSCs. Pargyline rescued the osteogenic differentiation ability of mouse BMMSCs under osteoporotic conditions by enhancing the dimethylation level of H3K4 at the promoter regions of osteogenesis-related genes. Moreover, pargyline partially rescued or prevented the osteoporotic conditions in aged or ovariectomized mouse models, respectively. By introducing the concept of epigenetic therapy into the field of osteoporosis, this study demonstrated that LSD1 inhibitors could improve the clinical practice of MSC-based bone tissue engineering and proposes their novel use to treat osteoporosis.

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“…The potential usefulness of cyclopropylamine inhibitors of MAO and LSD1 for treatment of depression [10][11][12] and cancer [4,[13][14][15][16][17], and the need for selective inhibition of the targets, have prompted the synthesis and evaluation of new inhibitors such as trans-1-substituted derivatives [9]. For the MAO enzymes, more derivatives of trans isomers have been studied, but cis-2phenylcyclopropylamine is only slightly less effective than the trans isomer [18][19][20].…”

Section: Introductionmentioning

confidence: 99%

cis‐cyclopropylamines as mechanism‐based inhibitors of monoamine oxidases

et al. 2015

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Cyclopropylamines, inhibitors of monoamine oxidases (MAO) and lysinespecific demethylase (LSD1), provide a useful structural scaffold for the design of mechanism-based inhibitors for treatment of depression and cancer. For new compounds with the less common cis relationship and with an alkoxy substituent at the 2-position of the cyclopropyl ring, the apparent affinity determined from docking experiments revealed little difference between the enantiomers. Using the racemate, kinetic parameters for the reversible and irreversible inhibition of MAO were determined. No inhibition of LSD1 was observed. For reversible inhibition, most compounds gave high IC50 values with MAO A, but sub-micromolar values with MAO B. After pre-incubation of the cyclopropylamine with the enzyme, the inhibition was irreversible for both MAO A and MAO B, and the activity was not restored by dilution. Spectral changes during inactivation of MAO A included bleaching at 456 nm and an increased absorbance at 400 nm, consistent with flavin modification. These derivatives are MAO B-selective irreversible inhibitors that do not show inhibition of LSD1. The best inhibitor was cis-N-benzyl-2-methoxycyclopropylamine, with an IC 50 of 5 nM for MAO B and 170 nM for MAO A after 30 min pre-incubation. This cis-cyclopropylamine is over 20-fold more effective than tranylcypromine, so may be studied as a lead for selective inhibitors of MAO B that do not inhibit LSD1.

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

Cited by 37 publications

References 33 publications

Monoamine Oxidase Inhibitors—Revisiting a Therapeutic Principle

Monoamine Oxidase Inhibitors—Revisiting a Therapeutic Principle

Lysine-specific demethylase 1 inhibitor rescues the osteogenic ability of mesenchymal stem cells under osteoporotic conditions by modulating H3K4 methylation

cis‐cyclopropylamines as mechanism‐based inhibitors of monoamine oxidases

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