PMID- 19198627
OWN - NLM
STAT- MEDLINE
DCOM- 20090407
LR  - 20240104
IS  - 1476-5594 (Electronic)
IS  - 0950-9232 (Linking)
VI  - 28
IP  - 12
DP  - 2009 Mar 26
TI  - Styryl sulfonyl compounds inhibit translation of cyclin D1 in mantle cell 
      lymphoma cells.
PG  - 1518-28
LID - 10.1038/onc.2008.502 [doi]
AB  - Mantle cell lymphoma (MCL) is characterized by the uncontrolled overexpression of 
      cyclin D1. Styryl sulfonyl compounds have shown potent antitumor activity against 
      MCL by inducing cell-cycle arrest and apoptosis. However, the exact molecular 
      mechanism by which these compounds function is yet to be elucidated. Here, we 
      show that the prototypical styryl sulfonyl compound ON 01910.Na decreased cyclin 
      D1 and c-Myc protein levels in MCL cells, whereas mRNA levels of cyclin D1 were 
      minimally affected. Notably, ON 01910.Na suppressed eukaryotic translation 
      initiation factor 4E (eIF4E)-mediated cyclin D1 mRNA translation, decreased 
      levels of phosphorylated Akt, mammalian target of Rapamycin (mTOR) and 
      eIF4E-binding protein (eIF4E-BP), lowered the cap site binding activity of eIF4E 
      and directly inhibited activity of phosphatidylinositol-3 kinase (PI-3K). 
      Analysis of apoptotic signaling pathways revealed that ON 01910.Na induced the 
      release of cytochrome c from mitochondria, altered expression of Bcl-2 family of 
      proteins and stimulated activation of caspases. Taken together, styryl sulfonyls 
      can cause a rapid decrease of cyclin D1 by blocking cyclin D1 mRNA translation 
      through inhibition of the PI-3K/Akt/mTOR/eIF4E-BP signaling pathway and 
      triggering a cytochrome c-dependent apoptotic pathway in MCL cells.
FAU - Prasad, A
AU  - Prasad A
AD  - Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical 
      School, Boston, MA 02215, USA.
FAU - Park, I-W
AU  - Park IW
FAU - Allen, H
AU  - Allen H
FAU - Zhang, X
AU  - Zhang X
FAU - Reddy, M V R
AU  - Reddy MV
FAU - Boominathan, R
AU  - Boominathan R
FAU - Reddy, E P
AU  - Reddy EP
FAU - Groopman, J E
AU  - Groopman JE
LA  - eng
GR  - 1 R43 CA134108-01A1/CA/NCI NIH HHS/United States
GR  - CA109820/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20090209
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (Antineoplastic Agents)
RN  - 0 (CCND1 protein, human)
RN  - 0 (Eukaryotic Initiation Factor-4E)
RN  - 0 (FOXO1 protein, human)
RN  - 0 (Forkhead Box Protein O1)
RN  - 0 (Forkhead Transcription Factors)
RN  - 0 (MYC protein, human)
RN  - 0 (Phosphoinositide-3 Kinase Inhibitors)
RN  - 0 (Proto-Oncogene Proteins c-myc)
RN  - 0 (Sulfones)
RN  - 136601-57-5 (Cyclin D1)
RN  - 67DOW7F9GL (ON 01910)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (raf Kinases)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - EC 2.7.12.2 (Mitogen-Activated Protein Kinase Kinases)
RN  - TE7660XO1C (Glycine)
SB  - IM
MH  - Antineoplastic Agents/*pharmacology
MH  - Apoptosis/drug effects
MH  - Cell Line, Tumor
MH  - Cyclin D1/*genetics
MH  - Eukaryotic Initiation Factor-4E/physiology
MH  - Extracellular Signal-Regulated MAP Kinases/physiology
MH  - Forkhead Box Protein O1
MH  - Forkhead Transcription Factors/metabolism
MH  - Glycine/*analogs & derivatives/pharmacology
MH  - Humans
MH  - Lymphoma, Mantle-Cell/*drug therapy/genetics/pathology
MH  - Mitogen-Activated Protein Kinase Kinases/physiology
MH  - Phosphoinositide-3 Kinase Inhibitors
MH  - Phosphorylation
MH  - Protein Biosynthesis/*drug effects
MH  - Protein Kinases/physiology
MH  - Proto-Oncogene Proteins c-akt/physiology
MH  - Proto-Oncogene Proteins c-myc/antagonists & inhibitors
MH  - Signal Transduction/drug effects
MH  - Sulfones/*pharmacology
MH  - TOR Serine-Threonine Kinases
MH  - p38 Mitogen-Activated Protein Kinases/physiology
MH  - raf Kinases/physiology
EDAT- 2009/02/10 09:00
MHDA- 2009/04/08 09:00
CRDT- 2009/02/10 09:00
PHST- 2009/02/10 09:00 [entrez]
PHST- 2009/02/10 09:00 [pubmed]
PHST- 2009/04/08 09:00 [medline]
AID - onc2008502 [pii]
AID - 10.1038/onc.2008.502 [doi]
PST - ppublish
SO  - Oncogene. 2009 Mar 26;28(12):1518-28. doi: 10.1038/onc.2008.502. Epub 2009 Feb 9.