PMID- 16053514
OWN - NLM
STAT- MEDLINE
DCOM- 20050921
LR  - 20220317
IS  - 1347-9032 (Print)
IS  - 1347-9032 (Linking)
VI  - 96
IP  - 7
DP  - 2005 Jul
TI  - HIV-1 protease inhibitor induces growth arrest and apoptosis of human prostate 
      cancer LNCaP cells in vitro and in vivo in conjunction with blockade of androgen 
      receptor STAT3 and AKT signaling.
PG  - 425-33
AB  - This study found that the HIV-1 protease inhibitor nelfinavir (NFV) induced 
      growth arrest and apoptosis of human prostate cancer cells (LNCaP, DU145 and PC-3 
      cells), as measured by MTT and terminal deoxyribonucleotide transferase-mediated 
      dUTP nick end labeling (TUNEL) assays, respectively, on the third day of culture. 
      In addition, NFV blocked androgen receptor (AR) signaling in association with 
      downregulation of nuclear levels of AR in LNCaP cells as measured by reporter 
      assay and western blot analysis. As expected, NFV downregulated the level of the 
      AR target molecule prostate specific antigen in these cells. Moreover, NFV 
      disrupted STAT3 signaling; protease inhibitors blocked interleukin-6-induced 
      phosphorylation of STAT3 and inhibited STAT3 DNA binding activity in LNCaP and 
      DU145 cells, as measured by western blot analysis and enzyme-linked immunosorbent 
      assay (ELISA), respectively. Furthermore, NFV blocked AKT signaling in prostate 
      cancer cells as measured by kinase assay with glycogen synthase 
      kinase-3alpha/beta as a substrate. Importantly, NFV inhibited the proliferation 
      of LNCaP cells presented as tumor xenografts in BALB/c nude mice without 
      side-effects. Taken together, NFV inhibited the proliferation of prostate cancer 
      cells in conjunction with blockade of signaling by AR, STAT3, and AKT, suggesting 
      that this family of compounds might be useful for the treatment of individuals 
      with prostate cancer.
FAU - Yang, Yang
AU  - Yang Y
AD  - Department of Hematology and Respiratory Medicine, Kochi University, Kochi 
      Medical School, Nankoku, Japan.
FAU - Ikezoe, Takayuki
AU  - Ikezoe T
FAU - Takeuchi, Tamotsu
AU  - Takeuchi T
FAU - Adachi, Yoshihiro
AU  - Adachi Y
FAU - Ohtsuki, Yuji
AU  - Ohtsuki Y
FAU - Takeuchi, Seisho
AU  - Takeuchi S
FAU - Koeffler, H Phillip
AU  - Koeffler HP
FAU - Taguchi, Hirokuni
AU  - Taguchi H
LA  - eng
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Cancer Sci
JT  - Cancer science
JID - 101168776
RN  - 0 (AR protein, human)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (HIV Protease Inhibitors)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Receptors, Androgen)
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (STAT3 protein, human)
RN  - 0 (Stat3 protein, mouse)
RN  - 0 (Trans-Activators)
RN  - EC 2.7.11.1 (AKT1 protein, human)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - HO3OGH5D7I (Nelfinavir)
SB  - IM
MH  - Animals
MH  - Apoptosis/*drug effects
MH  - Cell Line, Tumor
MH  - DNA-Binding Proteins/*antagonists & inhibitors/metabolism
MH  - Down-Regulation
MH  - HIV Protease Inhibitors/*pharmacology
MH  - Humans
MH  - In Vitro Techniques
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Nelfinavir/*pharmacology
MH  - Prostatic Neoplasms/*drug therapy
MH  - Protein Serine-Threonine Kinases/*antagonists & inhibitors/metabolism
MH  - Proto-Oncogene Proteins/*antagonists & inhibitors/metabolism
MH  - Proto-Oncogene Proteins c-akt
MH  - Receptors, Androgen/*drug effects
MH  - STAT3 Transcription Factor
MH  - Signal Transduction/drug effects
MH  - Trans-Activators/*antagonists & inhibitors/metabolism
EDAT- 2005/08/02 09:00
MHDA- 2005/09/22 09:00
CRDT- 2005/08/02 09:00
PHST- 2005/08/02 09:00 [pubmed]
PHST- 2005/09/22 09:00 [medline]
PHST- 2005/08/02 09:00 [entrez]
AID - CAS063 [pii]
AID - 10.1111/j.1349-7006.2005.00063.x [doi]
PST - ppublish
SO  - Cancer Sci. 2005 Jul;96(7):425-33. doi: 10.1111/j.1349-7006.2005.00063.x.