PMID- 19759193
OWN - NLM
STAT- MEDLINE
DCOM- 20091207
LR  - 20211020
IS  - 1460-2180 (Electronic)
IS  - 0143-3334 (Print)
IS  - 0143-3334 (Linking)
VI  - 30
IP  - 11
DP  - 2009 Nov
TI  - Selenium modifies the osteoblast inflammatory stress response to bone metastatic 
      breast cancer.
PG  - 1941-8
LID - 10.1093/carcin/bgp227 [doi]
AB  - Breast cancer frequently metastasizes to the skeleton resulting in bone 
      degradation due to osteoclast activation. Metastases also downregulate 
      differentiation and the bone-rebuilding function of osteoblasts. Moreover, cancer 
      cells trigger osteoblast inflammatory stress responses. Pro-inflammatory 
      mediators such as interleukin (IL)-6, monocyte chemoattractant protein-1 (MCP-1), 
      cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS), expressed by 
      osteoblasts (MC3T3-E1) stimulated with human breast cancer cell (MDA-MB-231) 
      conditioned medium, are pivotal to osteoclast activation and metastasis. Given 
      that these genes are regulated by nuclear factor-kappaB (NF-kappaB), a 
      redox-sensitive transcription factor, we hypothesized that selenium (Se) could 
      abrogate the inflammatory response to metastatic breast cancer cells by 
      modulating NF-kappaB. Caffeic acid phenethyl ester and parthenolide inhibited 
      NF-kappaB activation, as seen by gel shift assays and immunoblotting for p65 in 
      nuclear fractions, as well as decreased production of IL-6 and MCP-1. 
      Supplementation of MC3T3-E1 with methylseleninic acid (MSA) (0.5 microM to 4 
      microM) reduced the activation of NF-kappaB leading to a decrease in IL-6, MCP-1, 
      COX-2 and iNOS in response to MDA-MB-231 conditioned medium. Addition of MSA to 
      osteoblasts for as little as 15 min suppressed activation of NF-kappaB suggesting 
      that short-lived active metabolites might be involved. However, brief exposure to 
      MSA also brought about an increase in selenoprotein glutathione peroxidase 1. In 
      summary, our data indicate that the osteoblast response to metastatic breast 
      cancer cells is regulated by NF-kappaB activation, which can be effectively 
      suppressed by MSA either through short-lived active metabolites and/or 
      selenoproteins. Thus, Se supplementation may prevent the osteoblast inflammatory 
      response or dampen the vicious cycle established when breast cancer cells, 
      osteoblasts and osteoclasts interact.
FAU - Chen, Yu-Chi
AU  - Chen YC
AD  - Department of Biochemistry and Molecular Biology, 431 South Frear Building, Penn 
      State University, University Park, PA 16802, USA.
FAU - Sosnoski, Donna M
AU  - Sosnoski DM
FAU - Gandhi, Ujjawal H
AU  - Gandhi UH
FAU - Novinger, Leah J
AU  - Novinger LJ
FAU - Prabhu, K Sandeep
AU  - Prabhu KS
FAU - Mastro, Andrea M
AU  - Mastro AM
LA  - eng
GR  - R01 DK077152/DK/NIDDK NIH HHS/United States
GR  - R01 DK 077152/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20090916
PL  - England
TA  - Carcinogenesis
JT  - Carcinogenesis
JID - 8008055
RN  - 0 (Chemokine CCL2)
RN  - 0 (Culture Media, Conditioned)
RN  - 0 (Interleukin-6)
RN  - 0 (NF-kappa B)
RN  - 0 (Organoselenium Compounds)
RN  - 9900C6V162 (methylselenic acid)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
RN  - H6241UJ22B (Selenium)
SB  - IM
MH  - Animals
MH  - Bone Neoplasms/metabolism/prevention & control/secondary
MH  - Breast Neoplasms/*metabolism/pathology
MH  - Cell Communication/drug effects
MH  - Cell Differentiation/drug effects
MH  - Cell Line, Tumor
MH  - Chemokine CCL2/biosynthesis
MH  - Culture Media, Conditioned/pharmacology
MH  - Cyclooxygenase 2/metabolism
MH  - Female
MH  - Humans
MH  - Inflammation
MH  - Interleukin-6/biosynthesis
MH  - Mice
MH  - NF-kappa B/metabolism
MH  - Nitric Oxide Synthase Type II/biosynthesis
MH  - Organoselenium Compounds/*pharmacology
MH  - Osteoblasts/drug effects/*metabolism/*pathology
MH  - Selenium/*metabolism
PMC - PMC2791325
EDAT- 2009/09/18 06:00
MHDA- 2009/12/16 06:00
PMCR- 2010/11/01
CRDT- 2009/09/18 06:00
PHST- 2009/09/18 06:00 [entrez]
PHST- 2009/09/18 06:00 [pubmed]
PHST- 2009/12/16 06:00 [medline]
PHST- 2010/11/01 00:00 [pmc-release]
AID - bgp227 [pii]
AID - 10.1093/carcin/bgp227 [doi]
PST - ppublish
SO  - Carcinogenesis. 2009 Nov;30(11):1941-8. doi: 10.1093/carcin/bgp227. Epub 2009 Sep 
      16.