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


METHODS
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.


RESULTS
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.


CONCLUSIONS
The data obtained here indicated that AINs could induce apoptosis in PC3 cells through DNA strand breaks and activation of caspase-3.
Guo
Maowu
M
Department of Immunology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-0071, Japan.
Sato
Eimei
E
Jin
Aishun
A
Li
Xiang
X
Mori
Etsuko
E
Xu
Yong
Y
Mori
Tsuneatsu
T
D017209:Apoptosis / Q000502:physiology*; D018959:CD57 Antigens / Q000032:analysis*; D053148:Caspase 3; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D018920:Coculture Techniques; D004247:DNA / Q000378:metabolism; D004249:DNA Damage; D053938:DNA Fragmentation; D004789:Enzyme Activation / Q000502:physiology; D016193:G1 Phase; D006684:HLA-DR Antigens / Q000032:analysis*; D006801:Humans; D008297:Male; D009705:Nucleosides / Q000502:physiology*; D011471:Prostatic Neoplasms / Q000473:pathology / Q000503:physiopathology*; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism
D018959:CD57 Antigens; D061945:Caspase Inhibitors; D006684:HLA-DR Antigens; D009705:Nucleosides; D004247:DNA; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases