PMID- 28832545
OWN - NLM
STAT- MEDLINE
DCOM- 20180501
LR  - 20231112
IS  - 1660-3397 (Electronic)
IS  - 1660-3397 (Linking)
VI  - 15
IP  - 9
DP  - 2017 Aug 23
TI  - The Marine Natural Product Pseudopterosin Blocks Cytokine Release of 
      Triple-Negative Breast Cancer and Monocytic Leukemia Cells by Inhibiting NF-kappaB 
      Signaling.
LID - 10.3390/md15090262 [doi]
LID - 262
AB  - Pseudopterosins are a group of marine diterpene glycosides which possess an array 
      of biological activities including anti-inflammatory effects. However, despite 
      the striking in vivo anti-inflammatory potential, the underlying in vitro 
      molecular mode of action remains elusive. To date, few studies have examined 
      pseudopterosin effects on cancer cells. However, to our knowledge, no studies 
      have explored their ability to block cytokine release in breast cancer cells and 
      the respective bidirectional communication with associated immune cells. The 
      present work demonstrates that pseudopterosins have the ability to block the key 
      inflammatory signaling pathway nuclear factor kappaB (NF-kappaB) by inhibiting the 
      phosphorylation of p65 and IkappaB (nuclear factor of kappa light polypeptide gene 
      enhancer in B-cells inhibitor) in leukemia and in breast cancer cells, 
      respectively. Blockade of NF-kappaB leads to subsequent reduction of the production 
      of the pro-inflammatory cytokines interleukin-6 (IL-6), tumor necrosis factor 
      alpha (TNFalpha) and monocyte chemotactic protein 1 (MCP-1). Furthermore, 
      pseudopterosin treatment reduces cytokine expression induced by conditioned media 
      in both cell lines investigated. Interestingly, the presence of pseudopterosins 
      induces a nuclear translocation of the glucocorticoid receptor. When knocking 
      down the glucocorticoid receptor, the natural product loses the ability to block 
      cytokine expression. Thus, we hypothesize that pseudopterosins inhibit NF-kappaB 
      through activation of the glucocorticoid receptor in triple negative breast 
      cancer.
FAU - Sperlich, Julia
AU  - Sperlich J
AD  - Bio-Pharmaceutical Chemistry & Molecular Pharmacology, Faculty of Applied Natural 
      Sciences, Technische Hochschule Koeln, Chempark, 51368 Leverkusen, Germany. 
      julia.sperlich@th-koeln.de.
FAU - Kerr, Russell
AU  - Kerr R
AD  - Department of Chemistry, and Department of Biomedical Sciences, Atlantic 
      Veterinary College, University of Prince Edward Island, Charlottetown, PE C1A 
      4P3, Canada. rkerr@upei.ca.
FAU - Teusch, Nicole
AU  - Teusch N
AD  - Bio-Pharmaceutical Chemistry & Molecular Pharmacology, Faculty of Applied Natural 
      Sciences, Technische Hochschule Koeln, Chempark, 51368 Leverkusen, Germany. 
      nicole.teusch@th-koeln.de.
LA  - eng
PT  - Journal Article
DEP - 20170823
PL  - Switzerland
TA  - Mar Drugs
JT  - Marine drugs
JID - 101213729
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Biological Products)
RN  - 0 (CCL2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Cytokines)
RN  - 0 (Diterpenes)
RN  - 0 (Glycosides)
RN  - 0 (I-kappa B Proteins)
RN  - 0 (Interleukin-6)
RN  - 0 (NF-kappa B)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (pseudopterosins)
SB  - IM
MH  - Anti-Inflammatory Agents/pharmacology
MH  - B-Lymphocytes/drug effects
MH  - Biological Products/chemistry/*pharmacology
MH  - Cell Count
MH  - Chemokine CCL2/metabolism
MH  - Cytokines/*drug effects/metabolism
MH  - Diterpenes/chemistry/*pharmacology
MH  - Female
MH  - Glycosides/chemistry/*pharmacology
MH  - Humans
MH  - I-kappa B Proteins/drug effects/*metabolism
MH  - Interleukin-6/metabolism
MH  - Leukemia, Monocytic, Acute/*drug therapy
MH  - Marine Biology
MH  - NF-kappa B/*drug effects/metabolism
MH  - Phosphorylation/drug effects
MH  - Signal Transduction/drug effects
MH  - Triple Negative Breast Neoplasms/*drug therapy
MH  - Tumor Necrosis Factor-alpha/metabolism
PMC - PMC5618401
OTO - NOTNLM
OT  - IL-6
OT  - MCP-1
OT  - NF-kappaB
OT  - TNFalpha
OT  - breast cancer
OT  - cytokine release
OT  - glucocorticoid receptor
OT  - inflammation
OT  - p65
OT  - pseudopterosin
OT  - tumor microenvironment
COIS- The authors declare no conflict of interest.
EDAT- 2017/08/24 06:00
MHDA- 2018/05/02 06:00
PMCR- 2017/09/01
CRDT- 2017/08/24 06:00
PHST- 2017/05/16 00:00 [received]
PHST- 2017/08/14 00:00 [revised]
PHST- 2017/08/21 00:00 [accepted]
PHST- 2017/08/24 06:00 [entrez]
PHST- 2017/08/24 06:00 [pubmed]
PHST- 2018/05/02 06:00 [medline]
PHST- 2017/09/01 00:00 [pmc-release]
AID - md15090262 [pii]
AID - marinedrugs-15-00262 [pii]
AID - 10.3390/md15090262 [doi]
PST - epublish
SO  - Mar Drugs. 2017 Aug 23;15(9):262. doi: 10.3390/md15090262.