Auranofin Suppresses Plasminogen Activator Inhibitor-2 Expression through Annexin A5 Induction in Human Prostate Cancer Cells.
10.4062/biomolther.2016.223
- Author:
Dong Won SHIN
1
;
Yeo Jung KWON
;
Dong Jin YE
;
Hyoung Seok BAEK
;
Joo Eun LEE
;
Young Jin CHUN
Author Information
1. College of Pharmacy, Chung-Ang University, Seoul 06974, Republic of Korea. yjchun@cau.ac.kr
- Publication Type:Original Article
- Keywords:
Annexin A5;
Apoptosis;
Auranofin;
Plasminogen activator inhibitor-2
- MeSH:
Annexin A5*;
Antirheumatic Agents;
Apoptosis;
Auranofin*;
Blotting, Western;
Gene Expression;
Humans*;
Leukemia, Lymphocytic, Chronic, B-Cell;
Plasminogen Activator Inhibitor 2;
Plasminogen Activators*;
Plasminogen*;
Prostate*;
Prostatic Neoplasms*;
RNA, Small Interfering;
Statistics as Topic
- From:Biomolecules & Therapeutics
2017;25(2):177-185
- CountryRepublic of Korea
- Language:English
-
Abstract:
Auranofin has been developed as antirheumatic drugs, which is currently under clinical development for the treatment of chronic lymphocytic leukemia. Previous report showed that auranofin induced apoptosis by enhancement of annexin A5 expression in PC-3 cells. To understand the role of annexin A5 in auranofin-mediated apoptosis, we performed microarray data analysis to study annexin A5-controlled gene expression in annexin A5 knockdown PC-3 cells. Of differentially expressed genes, plasminogen activator inhibitor (PAI)-2 was increased by annexin A5 siRNA confirmed by qRT-PCR and western blot. Treatment with auranofin decreased PAI-2 and increased annexin A5 expression as well as promoting apoptosis. Furthermore, auranofin-induced apoptosis was recovered by annexin A5 siRNA but it was promoted by PAI-2 siRNA. Interestingly, knockdown of annexin A5 rescued PAI-2 expression suppressed by auranofin. Taken together, our study suggests that induction of annexin A5 by auranofin may enhance apoptosis through suppression of PAI-2 expression in PC-3 cells.
