PMID- 21072520
OWN - NLM
STAT- MEDLINE
DCOM- 20111003
LR  - 20181201
IS  - 1432-0843 (Electronic)
IS  - 0344-5704 (Linking)
VI  - 68
IP  - 2
DP  - 2011 Aug
TI  - Antitumor effects of (S)-HDAC42, a phenylbutyrate-derived histone deacetylase 
      inhibitor, in multiple myeloma cells.
PG  - 489-96
LID - 10.1007/s00280-010-1501-z [doi]
AB  - PURPOSE: Epigenetic agents are among the newly targeted therapeutic strategies 
      being studied with intense interest for patients with multiple myeloma. Here, we 
      demonstrate the antitumor activity of a phenylbutyrate-based histone deacetylase 
      (HDAC) inhibitor, (S)-HDAC42, and identify its possible targets in myeloma cells. 
      METHODS: The antiproliferative effect of (S)-HDAC42 was compared with 
      suberoylanilide hydroxamic acid (SAHA) in three myeloma cell lines, IM-9, 
      RPMI-8226, and U266. Flow cytometry and terminal transferase dUTP nick-end 
      labeling (TUNEL) assay were used to demonstrate the induction of apoptosis by 
      (S)-HDAC42. Moreover, the proposed mechanisms of action, such as modulation of 
      Akt, NF-kappaB pathway, and cell cycle-related proteins, were investigated by western 
      blotting. RESULTS: (S)-HDAC42 exhibited four- to sevenfold higher potency 
      relative to SAHA in suppressing myeloma cell viabilities. The apoptotic effect 
      induced by (S)-HDAC42 was through both intrinsic and extrinsic pathways, as 
      evidenced by increased cleavage of caspase-3, caspase-8, and caspase-9 and 
      release of cytochrome c from mitochondria. In addition to HDAC inhibition, 
      (S)-HDAC42 also disturbed signaling pathways governing cell survival, including 
      downregulating Akt phosphorylation and NF-kappaB signaling. The modulation of cell 
      cycle-related proteins by (S)-HDAC42 suggested its inhibitory effect on cell 
      cycle propagation. CONCLUSION: These data suggest the translational value of 
      (S)-HDAC42 in developing new therapeutic strategies for myeloma, which warrants 
      further investigations.
FAU - Bai, Li-Yuan
AU  - Bai LY
AD  - Graduate Institute of Clinical Medical Science, China Medical University, 
      Taichung, Taiwan.
FAU - Omar, Hany A
AU  - Omar HA
FAU - Chiu, Chang-Fang
AU  - Chiu CF
FAU - Chi, Zeng-Pang
AU  - Chi ZP
FAU - Hu, Jing-Lan
AU  - Hu JL
FAU - Weng, Jing-Ru
AU  - Weng JR
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20101112
PL  - Germany
TA  - Cancer Chemother Pharmacol
JT  - Cancer chemotherapy and pharmacology
JID - 7806519
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Histone Deacetylase Inhibitors)
RN  - 0 (Hydroxamic Acids)
RN  - 0 (Isoenzymes)
RN  - 0 (NF-kappa B)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (OSU-HDAC42 compound)
RN  - 0 (Phenylbutyrates)
RN  - 58IFB293JI (Vorinostat)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 3.4.22.- (Caspases)
SB  - IM
MH  - Antineoplastic Agents/*pharmacology
MH  - Apoptosis/*drug effects
MH  - Caspases/metabolism
MH  - Cell Cycle Proteins/metabolism
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects
MH  - Cell Survival/drug effects
MH  - Histone Deacetylase Inhibitors/*pharmacology
MH  - Humans
MH  - Hydroxamic Acids/pharmacology
MH  - Inhibitory Concentration 50
MH  - Isoenzymes/metabolism
MH  - Mitochondria/drug effects/enzymology
MH  - Multiple Myeloma/*drug therapy/pathology
MH  - NF-kappa B/metabolism
MH  - Neoplasm Proteins/metabolism
MH  - Phenylbutyrates/*pharmacology
MH  - Phosphorylation/drug effects
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Signal Transduction/drug effects
MH  - Vorinostat
EDAT- 2010/11/13 06:00
MHDA- 2011/10/04 06:00
CRDT- 2010/11/13 06:00
PHST- 2010/06/04 00:00 [received]
PHST- 2010/10/26 00:00 [accepted]
PHST- 2010/11/13 06:00 [entrez]
PHST- 2010/11/13 06:00 [pubmed]
PHST- 2011/10/04 06:00 [medline]
AID - 10.1007/s00280-010-1501-z [doi]
PST - ppublish
SO  - Cancer Chemother Pharmacol. 2011 Aug;68(2):489-96. doi: 
      10.1007/s00280-010-1501-z. Epub 2010 Nov 12.