PMID- 27106131
OWN - NLM
STAT- MEDLINE
DCOM- 20171106
LR  - 20210109
IS  - 1878-0261 (Electronic)
IS  - 1574-7891 (Print)
IS  - 1574-7891 (Linking)
VI  - 10
IP  - 7
DP  - 2016 Aug
TI  - Combination therapy induces unfolded protein response and cytoskeletal 
      rearrangement leading to mitochondrial apoptosis in prostate cancer.
PG  - 949-65
LID - S1574-7891(16)30014-X [pii]
LID - 10.1016/j.molonc.2016.03.007 [doi]
AB  - Development of therapeutic resistance is responsible for most prostate cancer 
      (PCa) related mortality. Resistance has been attributed to an acquired or 
      selected cancer stem cell phenotype. Here we report the histone deacetylase 
      inhibitor apicidin (APC) or ER stressor thapsigargin (TG) potentiate paclitaxel 
      (TXL)-induced apoptosis in PCa cells and limit accumulation of cancer stem cells. 
      TXL-induced responses were modulated in the presence of TG with increased 
      accumulation of cells at G1-phase, rearrangement of the cytoskeleton, and changes 
      in cytokine release. Cytoskeletal rearrangement was associated with modulation of 
      the cytoplasmic and mitochondrial unfolded protein response leading to 
      mitochondrial dysfunction and release of proapoptotic proteins from mitochondria. 
      TXL in combination with APC or TG enhanced caspase activation. Importantly, TXL 
      in combination with TG induced caspase activation and apoptosis in X-ray 
      resistant LNCaP cells. Increased release of transforming growth factor-beta 
      (TGF-beta) was observed while phosphorylated beta-catenin level was suppressed with TXL 
      combination treatments. This was accompanied by a decrease in the CD44(+)CD133(+) 
      cancer stem cell-like population, suggesting treatment affects cancer stem cell 
      properties. Taken together, combination treatment with TXL and either APC or TG 
      induces efficient apoptosis in both proliferating and cancer stem cells, 
      suggesting this therapeutic combination may overcome drug resistance and 
      recurrence in PCa.
CI  - Copyright (c) 2016 Federation of European Biochemical Societies. Published by 
      Elsevier B.V. All rights reserved.
FAU - Kumar, Sandeep
AU  - Kumar S
AD  - Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Elm 
      and Carlton Streets, Buffalo, NY 14263, USA.
FAU - Chaudhary, Ajay K
AU  - Chaudhary AK
AD  - Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Elm 
      and Carlton Streets, Buffalo, NY 14263, USA.
FAU - Kumar, Rahul
AU  - Kumar R
AD  - Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Elm 
      and Carlton Streets, Buffalo, NY 14263, USA.
FAU - O'Malley, Jordan
AU  - O'Malley J
AD  - Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Elm 
      and Carlton Streets, Buffalo, NY 14263, USA.
FAU - Dubrovska, Anna
AU  - Dubrovska A
AD  - OncoRay-National Center for Radiation Research in Oncology, Medical Faculty and 
      University Hospital Carl Gustav Carus, Technische Universitat Dresden and 
      Helmholtz-Zentrum Dresden-Rossendorf, Fetscherstrasse, Dresden, Germany; German 
      Cancer Consortium (DKTK) Dresden and German Cancer Research Center (DKFZ), 
      Heidelberg, Germany.
FAU - Wang, Xinjiang
AU  - Wang X
AD  - Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Elm 
      and Carlton Streets, Buffalo, NY 14263, USA.
FAU - Yadav, Neelu
AU  - Yadav N
AD  - Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Elm 
      and Carlton Streets, Buffalo, NY 14263, USA.
FAU - Goodrich, David W
AU  - Goodrich DW
AD  - Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Elm 
      and Carlton Streets, Buffalo, NY 14263, USA.
FAU - Chandra, Dhyan
AU  - Chandra D
AD  - Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Elm 
      and Carlton Streets, Buffalo, NY 14263, USA. Electronic address: 
      dhyan.chandra@roswellpark.org.
LA  - eng
GR  - P30 CA016056/CA/NCI NIH HHS/United States
GR  - R01 CA160685/CA/NCI NIH HHS/United States
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, Non-P.H.S.
DEP - 20160331
PL  - United States
TA  - Mol Oncol
JT  - Molecular oncology
JID - 101308230
RN  - 0 (HSP70 Heat-Shock Proteins)
RN  - 0 (Interleukin-8)
RN  - 0 (Peptides, Cyclic)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Transforming Growth Factor beta)
RN  - 0 (apicidin)
RN  - 0 (beta Catenin)
RN  - 67526-95-8 (Thapsigargin)
RN  - 82115-62-6 (Interferon-gamma)
RN  - EC 3.4.22.- (Caspases)
RN  - EC 3.4.24.- (Matrix Metalloproteinases)
RN  - P88XT4IS4D (Paclitaxel)
SB  - IM
MH  - Antineoplastic Combined Chemotherapy Protocols/pharmacology/*therapeutic use
MH  - *Apoptosis/drug effects/radiation effects
MH  - Caspases/metabolism
MH  - Cell Cycle Checkpoints/drug effects/radiation effects
MH  - Cell Death/drug effects/radiation effects
MH  - Cell Line, Tumor
MH  - Cytoskeleton/drug effects/*metabolism/radiation effects
MH  - Enzyme Activation/drug effects
MH  - G1 Phase/drug effects/radiation effects
MH  - G2 Phase/drug effects/radiation effects
MH  - HSP70 Heat-Shock Proteins/metabolism
MH  - Humans
MH  - Interferon-gamma/metabolism
MH  - Interleukin-8/metabolism
MH  - Male
MH  - Matrix Metalloproteinases/metabolism
MH  - Membrane Potential, Mitochondrial/drug effects/radiation effects
MH  - Mitochondria/drug effects/*metabolism/radiation effects
MH  - Neoplastic Stem Cells/drug effects/metabolism/pathology/radiation effects
MH  - Paclitaxel
MH  - Peptides, Cyclic/pharmacology/therapeutic use
MH  - Phosphorylation/drug effects
MH  - Prostatic Neoplasms/*drug therapy/*metabolism/pathology/radiotherapy
MH  - Reactive Oxygen Species/metabolism
MH  - Thapsigargin/pharmacology/therapeutic use
MH  - Transforming Growth Factor beta/metabolism
MH  - *Unfolded Protein Response/drug effects/radiation effects
MH  - X-Rays
MH  - beta Catenin/metabolism
PMC - PMC4972665
MID - NIHMS780222
OTO - NOTNLM
OT  - Anticancer drugs
OT  - Apoptosis
OT  - Combination therapy
OT  - Mitochondria
OT  - Prostate cancer
OT  - Unfolded protein response
EDAT- 2016/04/24 06:00
MHDA- 2017/11/07 06:00
PMCR- 2016/08/01
CRDT- 2016/04/24 06:00
PHST- 2016/01/13 00:00 [received]
PHST- 2016/03/13 00:00 [revised]
PHST- 2016/03/23 00:00 [accepted]
PHST- 2016/04/24 06:00 [entrez]
PHST- 2016/04/24 06:00 [pubmed]
PHST- 2017/11/07 06:00 [medline]
PHST- 2016/08/01 00:00 [pmc-release]
AID - S1574-7891(16)30014-X [pii]
AID - MOL22016107949 [pii]
AID - 10.1016/j.molonc.2016.03.007 [doi]
PST - ppublish
SO  - Mol Oncol. 2016 Aug;10(7):949-65. doi: 10.1016/j.molonc.2016.03.007. Epub 2016 
      Mar 31.