PMID- 12269771
OWN - NLM
STAT- MEDLINE
DCOM- 20030417
LR  - 20191106
IS  - 0361-090X (Print)
IS  - 0361-090X (Linking)
VI  - 26
IP  - 3
DP  - 2002
TI  - Inhibition of nuclear factor kappaB induces apoptosis following treatment with 
      tumor necrosis factor alpha and an antioxidant in human prostate cancer cells.
PG  - 229-37
AB  - Transforming growth factor beta-1 (TGFbeta-1) and tumor necrosis factor alpha 
      (TNF-alpha), an activator of nuclear factor kappa B (NF-kappaB), modulate 
      apoptosis and/or cell growth. This study was designed to investigate the activity 
      of NF-kappaB and its regulation of inhibitor of apoptosis gene (c-IAP2) in two 
      human prostate cancer cell lines, DU-145 (which is androgen unresponsive) and 
      ALVA-101 (which is moderately androgen responsive). These cells were treated with 
      and without various concentrations of a strong antioxidant, 
      pyrrolidinedithiocarbamate (PDTC), and TNF-alpha at various time intervals. 
      Following treatments, cell growth and apoptosis were determined by ELISA 
      techniques. NF-kappaB activity was determined by electrophoretic mobility shift 
      assay (EMSA), and c-IAP2 mRNA production was determined with Northern blot 
      analysis. PDTC treatment significantly reduced cell growth up to 80% in both 
      DU-145 and ALVA-101 cells. TNF-alpha and lower but not higher doses of PDTC 
      combined demonstrated an additive inhibition of cell growth in both cell lines. 
      Active NF-kappaB and c-IAP2 was blocked significantly following PDTC treatments, 
      whereas treatments with TNF-alpha alone showed increased NF-kappaB activity and 
      c-IAP2. However, when both PDTC and TNF-alpha were combined, nuclear presence of 
      NF-kappaB and c-IAP2 were reduced significantly (P < 0.05) to levels observed 
      with PDTC alone. In conclusion, the antioxidant, PDTC, appears to initiate 
      apoptosis by blocking cytoplasmic NF-kappaB translocation to the nucleus where it 
      normally activates the production of apoptosis-inhibitory proteins like c-IAP2. 
      Both TNF-alpha and PDTC alone cause apoptosis and reduce cell growth, but their 
      combined effects are additive in reducing cell growth of DU-145 and ALVA-101 
      human prostate cancer cells.
FAU - Gunawardena, Kushlani
AU  - Gunawardena K
AD  - Department of Medicine and Pathology, University of Utah School of Medicine, Salt 
      Lake City 84132, USA.
FAU - Murray, Darrell K
AU  - Murray DK
FAU - Swope, Richard E
AU  - Swope RE
FAU - Meikle, A Wayne
AU  - Meikle AW
LA  - eng
PT  - Journal Article
PL  - England
TA  - Cancer Detect Prev
JT  - Cancer detection and prevention
JID - 7704778
RN  - 0 (Antineoplastic Agents)
RN  - 0 (NF-kappa B)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Proteins)
RN  - 0 (Thiocarbamates)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 135467-92-4 (prolinedithiocarbamate)
RN  - 9DLQ4CIU6V (Proline)
SB  - IM
MH  - Antineoplastic Agents/*therapeutic use
MH  - Apoptosis/*drug effects
MH  - Computer Graphics
MH  - Humans
MH  - Male
MH  - NF-kappa B/*biosynthesis/drug effects
MH  - Neoplasm Proteins/*biosynthesis/drug effects
MH  - Proline/*analogs & derivatives/*therapeutic use
MH  - Prostatic Neoplasms/*drug therapy/metabolism/pathology
MH  - Protein Biosynthesis
MH  - Proteins/drug effects
MH  - Thiocarbamates/*therapeutic use
MH  - Tumor Cells, Cultured
MH  - Tumor Necrosis Factor-alpha/*therapeutic use
EDAT- 2002/09/25 06:00
MHDA- 2003/04/18 05:00
CRDT- 2002/09/25 06:00
PHST- 2002/09/25 06:00 [pubmed]
PHST- 2003/04/18 05:00 [medline]
PHST- 2002/09/25 06:00 [entrez]
AID - S0361-090X(02)00061-2 [pii]
AID - 10.1016/s0361-090x(02)00061-2 [doi]
PST - ppublish
SO  - Cancer Detect Prev. 2002;26(3):229-37. doi: 10.1016/s0361-090x(02)00061-2.