PMID- 19619938
OWN - NLM
STAT- MEDLINE
DCOM- 20100225
LR  - 20231213
IS  - 1872-7980 (Electronic)
IS  - 0304-3835 (Linking)
VI  - 288
IP  - 2
DP  - 2010 Feb 28
TI  - Rosmarinic acid sensitizes cell death through suppression of TNF-alpha-induced 
      NF-kappaB activation and ROS generation in human leukemia U937 cells.
PG  - 183-91
LID - 10.1016/j.canlet.2009.06.033 [doi]
AB  - Because tumor necrosis factor-alpha (TNF-alpha) is well-known to induce 
      inflammatory responses, thus its clinical use is limited in cancer treatment. 
      Rosmarinic acid (RA), a naturally occurring polyphenol flavonoid, has been 
      reported to inhibit TNF-alpha-induced NF-kappaB activation in human dermal 
      fibroblasts. However, the precise mechanisms of RA have not been well elucidated 
      in TNF-alpha-mediated anti-cancer therapy. In this study, we found that RA 
      treatment significantly sensitizes TNF-alpha-induced apoptosis in human leukemia 
      U937 cells through the suppression of nuclear transcription factor-kappaB 
      (NF-kappaB) and reactive oxygen species (ROS). Activation of caspases in response 
      to TNF-alpha was markedly increased by RA treatment. However, pretreatment with 
      the caspase-3 inhibitor, z-DEVD-fmk, was capable of significantly restoring cell 
      viability in response to combined treatment. RA also suppressed NF-kappaB 
      activation through inhibition of phosphorylation and degradation of IkappaBalpha, 
      and nuclear translocation of p50 and p65. This inhibition was correlated with 
      suppression of NF-kappaB-dependent anti-apoptotic proteins (IAP-1, IAP-2, and 
      XIAP). RA treatment also normalized TNF-alpha-induced ROS generation. 
      Additionally, ectopic Bcl-2 expressing U937 reversed combined treatment-induced 
      cell death, cytochrome c release into cytosol, and collapse of mitochondrial 
      potential. These results demonstrated that RA inhibits TNF-alpha-induced ROS 
      generation and NF-kappaB activation, and enhances TNF-alpha-induced apoptosis.
CI  - 2009 Elsevier Ireland Ltd. All rights reserved.
FAU - Moon, Dong-Oh
AU  - Moon DO
AD  - Department of Marine Life Sciences, Jeju National University, Republic of Korea.
FAU - Kim, Mun-Ock
AU  - Kim MO
FAU - Lee, Jae-Dong
AU  - Lee JD
FAU - Choi, Yung Hyun
AU  - Choi YH
FAU - Kim, Gi-Young
AU  - Kim GY
LA  - eng
PT  - Journal Article
DEP - 20090719
PL  - Ireland
TA  - Cancer Lett
JT  - Cancer letters
JID - 7600053
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Antioxidants)
RN  - 0 (Caspase Inhibitors)
RN  - 0 (Cinnamates)
RN  - 0 (Cysteine Proteinase Inhibitors)
RN  - 0 (Depsides)
RN  - 0 (I-kappa B Proteins)
RN  - 0 (Inhibitor of Apoptosis Proteins)
RN  - 0 (NF-kappa B)
RN  - 0 (NF-kappa B p50 Subunit)
RN  - 0 (NFKB1 protein, human)
RN  - 0 (NFKBIA protein, human)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (RELA protein, human)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Transcription Factor RelA)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 139874-52-5 (NF-KappaB Inhibitor alpha)
RN  - 9007-43-6 (Cytochromes c)
RN  - EC 3.4.22.- (Caspases)
SB  - IM
MH  - Active Transport, Cell Nucleus
MH  - Antineoplastic Agents/*pharmacology
MH  - Antioxidants/*pharmacology
MH  - Apoptosis/*drug effects
MH  - Caspase Inhibitors
MH  - Caspases/metabolism
MH  - Cell Survival/drug effects
MH  - Cinnamates/*pharmacology
MH  - Cysteine Proteinase Inhibitors/pharmacology
MH  - Cytochromes c/metabolism
MH  - Depsides/*pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Hep G2 Cells
MH  - Humans
MH  - I-kappa B Proteins/metabolism
MH  - Inhibitor of Apoptosis Proteins/metabolism
MH  - Leukemia/*metabolism/pathology
MH  - Membrane Potential, Mitochondrial/drug effects
MH  - NF-KappaB Inhibitor alpha
MH  - NF-kappa B/*metabolism
MH  - NF-kappa B p50 Subunit/metabolism
MH  - Oxidative Stress/drug effects
MH  - Phosphorylation
MH  - Proto-Oncogene Proteins c-bcl-2/genetics/metabolism
MH  - Reactive Oxygen Species/*metabolism
MH  - Recombinant Proteins/pharmacology
MH  - Signal Transduction/drug effects
MH  - Transcription Factor RelA/metabolism
MH  - Tumor Necrosis Factor-alpha/*pharmacology
MH  - U937 Cells
MH  - Rosmarinic Acid
EDAT- 2009/07/22 09:00
MHDA- 2010/02/26 06:00
CRDT- 2009/07/22 09:00
PHST- 2008/10/10 00:00 [received]
PHST- 2009/06/26 00:00 [revised]
PHST- 2009/06/26 00:00 [accepted]
PHST- 2009/07/22 09:00 [entrez]
PHST- 2009/07/22 09:00 [pubmed]
PHST- 2010/02/26 06:00 [medline]
AID - S0304-3835(09)00461-3 [pii]
AID - 10.1016/j.canlet.2009.06.033 [doi]
PST - ppublish
SO  - Cancer Lett. 2010 Feb 28;288(2):183-91. doi: 10.1016/j.canlet.2009.06.033. Epub 
      2009 Jul 19.