Biomol Ther.  2017 Mar;25(2):177-185. 10.4062/biomolther.2016.223.

Auranofin Suppresses Plasminogen Activator Inhibitor-2 Expression through Annexin A5 Induction in Human Prostate Cancer Cells

• Shin DW
• Kwon YJ
• Ye DJ
• Baek HS
• Lee JE
• Chun YJ

• KMID: 2375038
• DOI: http://doi.org/10.4062/biomolther.2016.223

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.

Keyword

Annexin A5; Apoptosis; Auranofin; Plasminogen activator inhibitor-2

MeSH Terms

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
Annexin A5
Antirheumatic Agents
Auranofin
Plasminogen
Plasminogen Activator Inhibitor 2
Plasminogen Activators
RNA, Small Interfering