Human prostate cancer cell death by novel anticancer compounds, apoptosis-inducing nucleosides from CD57+ HLA-DR(bright) natural suppressor cell line.

Abstract

We validated the induction of apoptosis in human prostate cancer PC3 cells by apoptosis-inducing nucleosides (AINs) released from the CD57(+)HLA-DR(bright)-natural suppressor (57.DR-NS) cell line. We analyzed the molecular signaling pathway during AINs-induced apoptosis in PC3 cells. Direct and indirect co-cultures between 57.DR-NS and PC3 cells were performed. AINs were isolated by high-performance liquid chromatography (HPLC) from 57.DR-NS cell cultures. Apoptosis in PC3 cells was analyzed by DNA fragmentation, sub-G(1) DNA content with flow cytometry, and terminal deoxynucleotide transferase-mediated dUTP nick end-labeling (TUNEL) method. The DNA strand breaks and activation of caspase-3 in PC3 cells were measured by DNA unwinding and flow cytometry assay. The 57.DR-NS cell line generated apoptosis in PC3 cells via AINs. AINs isolated from 57.DR-NS cell cultures induced apoptosis in PC3 cells. Furthermore, we found DNA strand breaks followed by activation of caspase-3 during AINs-induced apoptosis in PC3 cells. The data obtained here indicated that AINs could induce apoptosis in PC3 cells through DNA strand breaks and activation of caspase-3.