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Pyrrolidine dithiocarbamate inhibits nuclear factor-κB pathway activation, and regulates adhesion, migration, invasion and apoptosis of endometriotic stromal cells.
Mol Hum Reprod. 2011 Mar; 17(3):175-81.MH

Abstract

The activation of nuclear factor-κB (NF-κB) has been implicated in the development and progression of endometriosis. The aim of this study is to investigate the potential application of pyrrolidine dithiocarbamate (PDTC), a potent NF-κB inhibitor, in the treatment of endometriosis. NF-κB-DNA-binding activity, IκB phosphorylation and expression of nuclear p65 protein in endometriotic ectopic stromal cells (EcSCs), endometriotic eutopic stromal cells (EuSCs) and normal endometrial stromal cells (NESCs) were detected by electrophoretic mobility shift assay and western blot analysis. Adhesion, migration, invasion and apoptosis of EcSCs were observed by means of adhesion, migration, invasion and terminal deoxynucleotidyl transferase-mediated dUDP nick-end labeling assay, respectively. Gene and protein expressions of CD44s, matrix metalloproteinase (MMP)-2, MMP-9 and survivin in EcSCs were measured by RT-PCR and western blot analysis. The results showed that PDTC in the absence or presence of interleukin (IL)-1β showed stronger inhibitory effects on NF-κB-DNA-binding activity, IκB phosphorylation and expression of nuclear p65 protein in EcSCs than those in EuSCs or NESCs. PDTC enhanced apoptosis, and suppressed IL-1β-induced cellular adhesion, migration and invasion of EcSCs. Pretreatment of EcSCs with PDTC attenuated IL-1β-induced expressions of CD44s, MMP-2, MMP-9 and survivin at gene and protein levels. All these findings suggest that PDTC induces apoptosis and down-regulates adhesion, migration and invasion of EcSCs through the suppression of various molecules. Therefore, PDTC could be used as a therapeutic agent for the treatment of endometriosis.

Authors+Show Affiliations

Department of Obstetrics and Gynecology, Affiliated Hospital of Medical College of Qingdao University, Qingdao, Shandong, China. xzmzjj@163.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

21030494

Citation

Zhang, Jing-jing, et al. "Pyrrolidine Dithiocarbamate Inhibits Nuclear factor-κB Pathway Activation, and Regulates Adhesion, Migration, Invasion and Apoptosis of Endometriotic Stromal Cells." Molecular Human Reproduction, vol. 17, no. 3, 2011, pp. 175-81.
Zhang JJ, Xu ZM, Zhang CM, et al. Pyrrolidine dithiocarbamate inhibits nuclear factor-κB pathway activation, and regulates adhesion, migration, invasion and apoptosis of endometriotic stromal cells. Mol Hum Reprod. 2011;17(3):175-81.
Zhang, J. J., Xu, Z. M., Zhang, C. M., Dai, H. Y., Ji, X. Q., Wang, X. F., & Li, C. (2011). Pyrrolidine dithiocarbamate inhibits nuclear factor-κB pathway activation, and regulates adhesion, migration, invasion and apoptosis of endometriotic stromal cells. Molecular Human Reproduction, 17(3), 175-81. https://doi.org/10.1093/molehr/gaq090
Zhang JJ, et al. Pyrrolidine Dithiocarbamate Inhibits Nuclear factor-κB Pathway Activation, and Regulates Adhesion, Migration, Invasion and Apoptosis of Endometriotic Stromal Cells. Mol Hum Reprod. 2011;17(3):175-81. PubMed PMID: 21030494.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pyrrolidine dithiocarbamate inhibits nuclear factor-κB pathway activation, and regulates adhesion, migration, invasion and apoptosis of endometriotic stromal cells. AU - Zhang,Jing-jing, AU - Xu,Zhi-ming, AU - Zhang,Chun-mei, AU - Dai,Hong-ying, AU - Ji,Xin-qiang, AU - Wang,Xu-fu, AU - Li,Chao, Y1 - 2010/10/28/ PY - 2010/10/30/entrez PY - 2010/10/30/pubmed PY - 2011/6/24/medline SP - 175 EP - 81 JF - Molecular human reproduction JO - Mol Hum Reprod VL - 17 IS - 3 N2 - The activation of nuclear factor-κB (NF-κB) has been implicated in the development and progression of endometriosis. The aim of this study is to investigate the potential application of pyrrolidine dithiocarbamate (PDTC), a potent NF-κB inhibitor, in the treatment of endometriosis. NF-κB-DNA-binding activity, IκB phosphorylation and expression of nuclear p65 protein in endometriotic ectopic stromal cells (EcSCs), endometriotic eutopic stromal cells (EuSCs) and normal endometrial stromal cells (NESCs) were detected by electrophoretic mobility shift assay and western blot analysis. Adhesion, migration, invasion and apoptosis of EcSCs were observed by means of adhesion, migration, invasion and terminal deoxynucleotidyl transferase-mediated dUDP nick-end labeling assay, respectively. Gene and protein expressions of CD44s, matrix metalloproteinase (MMP)-2, MMP-9 and survivin in EcSCs were measured by RT-PCR and western blot analysis. The results showed that PDTC in the absence or presence of interleukin (IL)-1β showed stronger inhibitory effects on NF-κB-DNA-binding activity, IκB phosphorylation and expression of nuclear p65 protein in EcSCs than those in EuSCs or NESCs. PDTC enhanced apoptosis, and suppressed IL-1β-induced cellular adhesion, migration and invasion of EcSCs. Pretreatment of EcSCs with PDTC attenuated IL-1β-induced expressions of CD44s, MMP-2, MMP-9 and survivin at gene and protein levels. All these findings suggest that PDTC induces apoptosis and down-regulates adhesion, migration and invasion of EcSCs through the suppression of various molecules. Therefore, PDTC could be used as a therapeutic agent for the treatment of endometriosis. SN - 1460-2407 UR - https://www.unboundmedicine.com/medline/citation/21030494/Pyrrolidine_dithiocarbamate_inhibits_nuclear_factor_κB_pathway_activation_and_regulates_adhesion_migration_invasion_and_apoptosis_of_endometriotic_stromal_cells_ L2 - https://academic.oup.com/molehr/article-lookup/doi/10.1093/molehr/gaq090 DB - PRIME DP - Unbound Medicine ER -