title: Inhibition of LSD1 by Pargyline inhibited process of EMT and delayed progression of prostate cancer in vivo.
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.
authors.affiliation: Department of Urology, Renmin Hospital of Wuhan University, Wuhan University, Jiefang Road 238, Wuhan 430060, Hubei, PR China.
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Urology, Renmin Hospital of Wuhan University, Wuhan University, Jiefang Road 238, Wuhan 430060, Hubei, PR China. Electronic address: doctlxh@163.com.
authors.forename: Xiuheng
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Urology, Renmin Hospital of Wuhan University, Wuhan University, Jiefang Road 238, Wuhan 430060, Hubei, PR China.
authors.forename: Jia
authors.initials: J
authors.lastname: Guo
authors.affiliation: Department of Urology, Renmin Hospital of Wuhan University, Wuhan University, Jiefang Road 238, Wuhan 430060, Hubei, PR China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Weng
authors.affiliation: Department of Urology, Renmin Hospital of Wuhan University, Wuhan University, Jiefang Road 238, Wuhan 430060, Hubei, PR China.
authors.forename: Guanjun
authors.initials: G
authors.lastname: Jiang
authors.affiliation: Department of Urology, Renmin Hospital of Wuhan University, Wuhan University, Jiefang Road 238, Wuhan 430060, Hubei, PR China.
authors.forename: Zhishun
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Urology, Renmin Hospital of Wuhan University, Wuhan University, Jiefang Road 238, Wuhan 430060, Hubei, PR China.
authors.forename: Li
authors.initials: L
authors.lastname: He
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D015820:Cadherins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D018450:Disease Progression; D058492:Drug Repositioning; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects* / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D056466:Histone Demethylases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D010293:Pargyline / Q000494:pharmacology*; D017430:Prostate-Specific Antigen / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014746:Vimentin / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D000959:Antihypertensive Agents; D000970:Antineoplastic Agents; D015820:Cadherins; C489083:Cdh2 protein, mouse; D004791:Enzyme Inhibitors; D011944:Receptors, Androgen; D014746:Vimentin; D010293:Pargyline; D056466:Histone Demethylases; C504076:KDM1a protein, mouse; D017430:Prostate-Specific Antigen
keywords: Androgen deprivation therapy; Castration resistant prostate cancer; Epithelial–mesenchymal transition; LSD1; Pargyline