Inhibition of LSD1 by Pargyline inhibited process of EMT and delayed progression of prostate cancer in vivo.
Biochem Biophys Res Commun
; 467(2): 310-5, 2015 Nov 13.
Article
em En
| MEDLINE
| ID: mdl-26435505
ABSTRACT
Recently, lysine-specific demethylase 1 (LSD1) was identified as the first histone demethylase. LSD1 interacted with androgen receptor (AR) and promoted androgen-dependent transcription of target genes, such as PSA, by ligand-induced demethylation of mono- and dimethylated histone H3 at Lys 9 (H3K9). Meanwhile, the phenomenon of epithelial-mesenchymal transition (EMT) had received considerable attention in tumor recurrence and metastasis. This study examined the effect of Pargyline (an inhibitor of LSD1) on the process of EMT in vitro and in vivo. SCID mice were injected subcutaneously with LNCap cells. Pargyline was given intraperitoneally or not after castration (implemented with Bilateral orchidectomy), then PSA levels in serum and tumor were determined to assess time to androgen-independent progression. The results showed that LSD1 expression was up-regulated when PCa progressed to Castration Resistant Prostate Cancer (CRPC). Pargyline reduced LNCap cells migration and invasion ability, and inhibited the process of EMT by up-regulating expression of E-cadherin, and down-regulating expressions of N-cadherin and Vimentin in vitro and in vivo. Although, Pargyline did not change the level of AR, it reduced PSA expression both in vitro and in vivo. Furthermore, Pargyline delayed prostate cancer transition from androgen-dependent to androgen-independent state (CRPC). These findings indicated that inhibition of LSD1 might be a promise adjunctive therapy with androgen deprivation therapy (ADT) for locally advanced or metastatic prostate cancer.
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MEDLINE
Assunto principal:
Pargilina
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Inibidores Enzimáticos
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Histona Desmetilases
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Transição Epitelial-Mesenquimal
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Neoplasias de Próstata Resistentes à Castração
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Antineoplásicos
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article