PMID- 20623631
OWN - NLM
STAT- MEDLINE
DCOM- 20100915
LR  - 20211203
IS  - 1097-0045 (Electronic)
IS  - 0270-4137 (Linking)
VI  - 70
IP  - 12
DP  - 2010 Sep 1
TI  - Methoxychalcone induces cell-cycle arrest and apoptosis in human 
      hormone-resistant prostate cancer cells through PI 3-kinase-independent 
      inhibition of mTOR pathways.
PG  - 1295-306
LID - 10.1002/pros.21165 [doi]
AB  - BACKGROUND: Chalcones are contained in fruits and vegetables, and have been 
      suggested to display anticancer activities. In this study, the anticancer 
      mechanism of WJ9708011 (a methoxychalcone derivative) was delineated in human 
      prostate cancer cells. METHOD: Cell proliferation was examined by sulforhodamine 
      B and clonogenic assays. Cell-cycle progression and mitochondrial membrane 
      potential (DeltaPsi(m)) were detected by flow cytometric analysis. Expressions of 
      protein and mRNA were detected by Western blot and RT-PCR technique, 
      respectively. The protein synthesis was examined by [(3)H]leucine incorporation 
      assay. The overexpression or knockdown techniques for specific target protein 
      were also used in this study. RESULTS: WJ9708011 induced time- and 
      concentration-dependent G1 arrest of the cell cycle and subsequent apoptosis in 
      human prostate cancer cells. The G1-arrest effect was confirmed by down-regulated 
      expressions of several G1-phase regulators, including cyclin D1, cyclin E, 
      cyclin-dependent kinase (Cdk)-4, Cdk2, phospho-RB, E2F-1, and Cdc25A. The mRNA 
      expressions of cyclin D1 and cyclin E were also inhibited through the suppression 
      of NF-kappaB. WJ9708011 blocked the protein synthesis and inhibited mammalian 
      target of rapamycin (mTOR) signaling pathways. The suppression of mTOR pathways 
      were irrespective of Akt- and AMPK-activated protein kinase (AMPK), but were 
      attributed to mitochondrial stress, in which the down-regulation of survivin 
      protein level may play a crucial role. CONCLUSIONS: The data suggest that 
      WJ9708011 induces transcriptional and translational suppression of cell-cycle 
      regulators that might be through Akt- and AMPK-independent loss of DeltaPsi(m) 
      and inhibition of mTOR signaling pathway, leading to G1 arrest of the cell cycle 
      and subsequent apoptotic cell death.
CI  - (c) 2010 Wiley-Liss, Inc.
FAU - Sun, Yu-Wei
AU  - Sun YW
AD  - School of Pharmacy, National Taiwan University, Taipei, Taiwan.
FAU - Huang, Wei-Jan
AU  - Huang WJ
FAU - Hsiao, Che-Jen
AU  - Hsiao CJ
FAU - Chen, Yi-Cheng
AU  - Chen YC
FAU - Lu, Pin-Hsuan
AU  - Lu PH
FAU - Guh, Jih-Hwa
AU  - Guh JH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Prostate
JT  - The Prostate
JID - 8101368
RN  - 0 (Chalcones)
RN  - 0 (DNA Primers)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Phosphoinositide-3 Kinase Inhibitors)
RN  - 0 (RNA, Neoplasm)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Reactive Oxygen Species)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Apoptosis/drug effects
MH  - Cell Cycle/*drug effects
MH  - Cell Division/drug effects
MH  - Chalcones/*pharmacology
MH  - DNA Damage
MH  - DNA Primers
MH  - DNA Repair
MH  - Humans
MH  - Intracellular Signaling Peptides and Proteins/*antagonists & inhibitors
MH  - Male
MH  - Membrane Potentials/drug effects
MH  - Mitochondria/drug effects/physiology
MH  - *Phosphoinositide-3 Kinase Inhibitors
MH  - Prostatic Neoplasms/genetics/*pathology
MH  - Protein Serine-Threonine Kinases/*antagonists & inhibitors
MH  - RNA, Neoplasm/genetics
MH  - RNA, Small Interfering/genetics
MH  - Reactive Oxygen Species/metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - TOR Serine-Threonine Kinases
MH  - Tumor Cells, Cultured/drug effects/pathology
MH  - Tumor Stem Cell Assay/methods
EDAT- 2010/07/14 06:00
MHDA- 2010/09/17 06:00
CRDT- 2010/07/13 06:00
PHST- 2010/07/13 06:00 [entrez]
PHST- 2010/07/14 06:00 [pubmed]
PHST- 2010/09/17 06:00 [medline]
AID - 10.1002/pros.21165 [doi]
PST - ppublish
SO  - Prostate. 2010 Sep 1;70(12):1295-306. doi: 10.1002/pros.21165.