Role of Clusterin and Tumor Necrosis Factor Receptors on the Apoptosis of Prostate Cancer Cells

Abstract

Purpose: In prostate cancer, the anti-apoptotic mechanism of sulfated glycoprotein-2 (clusterin) against tumor necrosis factor-alpha (TNF-α) receptors and the action of type 2 TNF-α receptor (TNFR2) were investigated. Materials and Methods: TNF-α, agonistic-TNF type 1 receptor (TNFR1) antibody, agonistic-TNF-R2 antibody and their combination were treated in PC3 cell line with or without anti-clusterin. Cytotoxicity was assessed by trypan blue dye exclusion assay. By using flowcytometric analysis, the exact amount of apoptosis and their changes were assessed. Results: Apoptosis was significantly increased in both agonistic-TNFR1 antibody and TNF-α treated cases after blocking the activity of clusterin. The more the anti-clusterin antibody added, the more the apoptosis occurred. The increase of total apoptosis was greater in TNF-α treated cells than in agonistic-TNFR1 antibody treated ones. However, there was no increase of apoptosis in agonistic-TNFR2 antibody and TNF-α with agonistic-TNFR2 antibody treated cases, respectively. Conclusions: Clusterin prevents TNF-α induced apoptosis by affecting TNFR1. The difference in degree of apoptosis between agonistic-TNFR1 antibody treated cells and TNF-α treated ones suggests the possibility of the action of TNFR2. It may be associated with affinity of TNF-α to the tumor cell surface.