PMID- 25111376
OWN - NLM
STAT- MEDLINE
DCOM- 20141101
LR  - 20161125
IS  - 1097-0045 (Electronic)
IS  - 0270-4137 (Linking)
VI  - 74
IP  - 14
DP  - 2014 Oct
TI  - Down-modulation of Bcl-2 sensitizes PTEN-mutated prostate cancer cells to 
      starvation and taxanes.
PG  - 1411-22
LID - 10.1002/pros.22857 [doi]
AB  - BACKGROUND: The critical role of PTEN in regulating the PI3K/Akt/mTOR signaling 
      pathway raises the possibility that targeting downstream effectors of the PI3K 
      pathway, such as Bcl-2, might be an effective anti-proliferative strategy for 
      PTEN-deficient prostate cancer cells. METHODS: Four prostate cancer cell lines 
      (LNCaP, PC3, DU145, 22Rv1) were assayed for their levels of total Akt and Ser473 
      phosphorylated Akt (p-Akt) by Western Blotting; their growth rates and 
      sensitivity to different doses of paclitaxel were determined by cell counts after 
      Trypan Blue dye exclusion assay. Cells were subjected to different combinations 
      of starvation (growth factors and/or aminoacids withdrawal), paclitaxel treatment 
      and Bcl-2 silencing by siRNA. Cell viability was evaluated by Trypan Blue dye 
      exclusion assay, Propidium Iodide (PI) and Annexin-V/PI staining. RESULTS: We 
      assessed the sensitivity of different prostate cancer cell lines to starvation 
      and we observed a differential response correlated to the levels of Akt 
      activation. The four prostate cancer cell lines also showed different sensitivity 
      to taxol treatments; LNCaP and 22Rv1 cells were more resistant to paclitaxel than 
      DU145 and PC3 cells. Combining taxol with growth factors and aminoacids 
      deprivation leaded to a more than additive reduction of cell viability compared 
      to single treatments in PTEN-mutant LNCaP cells. Down-modulation of 
      anti-apoptotic Bcl-2 protein by siRNA sensitized LNCaP cells to taxanes and 
      starvation induced cell death. CONCLUSIONS: Silencing Bcl-2 in PTEN-mutated 
      prostate cancer cells enhances the apoptotic effects of combined starvation and 
      taxol treatments, indicating that inhibition of Bcl-2 may be of significant value 
      in PTEN-mutant tumor therapy.
CI  - (c) 2014 Wiley Periodicals, Inc.
FAU - Calastretti, Angela
AU  - Calastretti A
AD  - Department of Medical Biotechnology and Translational Medicine, Universita degli 
      Studi di Milano, Milan, Italy.
FAU - Gatti, Giuliana
AU  - Gatti G
FAU - Quaresmini, Carolina
AU  - Quaresmini C
FAU - Bevilacqua, Annamaria
AU  - Bevilacqua A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140811
PL  - United States
TA  - Prostate
JT  - The Prostate
JID - 8101368
RN  - 0 (Antineoplastic Agents, Phytogenic)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - EC 3.1.3.67 (PTEN Phosphohydrolase)
RN  - EC 3.1.3.67 (PTEN protein, human)
RN  - P88XT4IS4D (Paclitaxel)
SB  - IM
MH  - Antineoplastic Agents, Phytogenic/pharmacology
MH  - Cell Line, Tumor
MH  - Down-Regulation
MH  - Humans
MH  - Male
MH  - Mutation
MH  - PTEN Phosphohydrolase/*genetics/metabolism
MH  - Paclitaxel/*pharmacology
MH  - Prostatic Neoplasms/*drug therapy/genetics/*metabolism
MH  - Proto-Oncogene Proteins c-bcl-2/genetics/*metabolism
OTO - NOTNLM
OT  - Akt
OT  - Bcl-2
OT  - PTEN
OT  - chemosensitization
OT  - nutrient starvation
OT  - taxanes
EDAT- 2014/08/12 06:00
MHDA- 2014/11/02 06:00
CRDT- 2014/08/12 06:00
PHST- 2014/04/07 00:00 [received]
PHST- 2014/06/17 00:00 [accepted]
PHST- 2014/08/12 06:00 [entrez]
PHST- 2014/08/12 06:00 [pubmed]
PHST- 2014/11/02 06:00 [medline]
AID - 10.1002/pros.22857 [doi]
PST - ppublish
SO  - Prostate. 2014 Oct;74(14):1411-22. doi: 10.1002/pros.22857. Epub 2014 Aug 11.