PMID- 15172129
OWN - NLM
STAT- MEDLINE
DCOM- 20040803
LR  - 20161124
IS  - 0304-3835 (Print)
IS  - 0304-3835 (Linking)
VI  - 210
IP  - 1
DP  - 2004 Jul 8
TI  - A new screening system for proliferation-independent anti-cancer agents.
PG  - 119-24
AB  - An in vitro screen for identification of novel anti-cancer agents, which can 
      induce proliferation-independent apoptosis of prostate cancer (PCA) cells, is 
      required, since the proliferative growth fraction of human prostate cancers in 
      patients is usually <10%. This is possible using the PCA cell line LNCaP, which 
      can be permanently transdifferentiated into a quiescent neuroendocrine (NE) 
      phenotype without undergoing apoptosis by the cytokine interleukine-6 (IL-6). 
      Transdifferentiation of LNCaP cells into a NE phenotype was documented using 
      western blot analysis and immunohistochemistry for the NE markers, 
      neuron-specific enolase (NSE) and beta III tubulin. Accumulation of NE cells in 
      the G0 phase of the cell cycle was demonstrated by Ki-67 immunohistochemistry. 
      The effects of paclitaxel, vinblastine and thapsigargin (TG) on viability and 
      apoptosis of NE and LNCaP cells were assessed by trypan blue exclusion and 4', 
      6-diamidino-2-phenylindole nuclear staining assays. In proliferating LNCaP cells, 
      there was a significant decrease in viable cells after 48 h exposure to 
      paclitaxel and vinblastine and a dramatic increase of apoptosis as compared with 
      the controls. On the other hand, treatment with paclitaxel or vinblastine 
      decreased the viability of NE cells only slightly without markedly increasing 
      their rate of apoptosis compared to controls. In contrast, both LNCaP and NE 
      cells showed a significant and comparable decrease in cell viability and similar 
      high levels of apoptosis when treated with TG. These results demonstrate that 
      terminally transdifferentiated NE cells represent a useful in vitro screening 
      system for identification of novel anti-cancer agents, like TG, that can induce 
      apoptosis without requiring proliferation.
CI  - Copyright 2004 Elsevier Ireland Ltd.
FAU - Horiatis, Dimitris
AU  - Horiatis D
AD  - Division of Medical Oncology, USC/Norris Comprehensive Cancer Center, University 
      of Southern California, 1441 Eastlake Avenue, Suite 3449, Los Angeles, CA 90033, 
      USA.
FAU - Wang, Qingcai
AU  - Wang Q
FAU - Pinski, Jacek
AU  - Pinski J
LA  - eng
PT  - Journal Article
PL  - Ireland
TA  - Cancer Lett
JT  - Cancer letters
JID - 7600053
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Ki-67 Antigen)
RN  - 5V9KLZ54CY (Vinblastine)
RN  - 67526-95-8 (Thapsigargin)
RN  - P88XT4IS4D (Paclitaxel)
SB  - IM
MH  - Antineoplastic Agents/*pharmacology
MH  - Apoptosis/*drug effects
MH  - Cell Differentiation/*drug effects
MH  - Cell Survival/drug effects
MH  - Drug Evaluation, Preclinical
MH  - Humans
MH  - Immunoenzyme Techniques
MH  - Ki-67 Antigen/metabolism
MH  - Male
MH  - Neurosecretory Systems/*drug effects/metabolism/pathology
MH  - Paclitaxel/pharmacology
MH  - Prostatic Neoplasms/*metabolism/pathology
MH  - Resting Phase, Cell Cycle/drug effects
MH  - Thapsigargin/pharmacology
MH  - Tumor Cells, Cultured
MH  - Vinblastine/pharmacology
EDAT- 2004/06/03 05:00
MHDA- 2004/08/04 05:00
CRDT- 2004/06/03 05:00
PHST- 2003/10/30 00:00 [received]
PHST- 2004/01/13 00:00 [revised]
PHST- 2004/01/16 00:00 [accepted]
PHST- 2004/06/03 05:00 [pubmed]
PHST- 2004/08/04 05:00 [medline]
PHST- 2004/06/03 05:00 [entrez]
AID - S0304383504001594 [pii]
AID - 10.1016/j.canlet.2004.01.037 [doi]
PST - ppublish
SO  - Cancer Lett. 2004 Jul 8;210(1):119-24. doi: 10.1016/j.canlet.2004.01.037.