PMID- 19768141
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20100609
LR  - 20220321
IS  - 1365-182X (Print)
IS  - 1477-2574 (Electronic)
IS  - 1365-182X (Linking)
VI  - 11
IP  - 5
DP  - 2009 Aug
TI  - Anti-inflammatory effects of the Nigella sativa seed extract, thymoquinone, in 
      pancreatic cancer cells.
PG  - 373-81
LID - 10.1111/j.1477-2574.2009.00059.x [doi]
AB  - BACKGROUND: Both hereditary and sporadic forms of chronic pancreatitis are 
      associated with an increased risk of developing pancreatic ductal adenocarcinoma 
      (PDA). Inflammation has been identified as a significant factor in the 
      development of solid tumour malignancies. We have recently shown that 
      thymoquinone (Tq), the major constituent of Nigella sativa oil extract, induced 
      apoptosis and inhibited proliferation in PDA cells. Tq also increased p21 WAF1 
      expression, inhibited histone deacetylase (HDAC) activity, and induced histone 
      hyperacetylation. HDAC inhibitors have been shown to ameliorate 
      inflammation-associated cancer. In this study, we evaluated the anti-inflammatory 
      potential of Tq in PDA cells in comparison with that of a specific HDAC 
      inhibitor, trichostatin A (TSA). METHODS: PDA cells were treated with or without 
      Tq (25-75 microM), with or without pre-treatment of tumour necrosis factor 
      (TNF)-alpha (25 ng/ml). The effect of Tq on the expression of different 
      proinflammatory cytokines and chemokines was analysed by real-time polymerase 
      chain reaction (PCR). Luciferase-labelled promoter studies evaluated the effect 
      of Tq on the transcription of monocyte chemoattractant protein-1 (MCP-1) and 
      nuclear factor-kappaB (NF-kappaB). The effect of Tq on the constitutive and 
      TNF-alpha-induced activation and nuclear translocation of NF-kappaB was examined 
      by ELISA and immunohistochemistry. RESULTS: Tq dose- and time-dependently 
      significantly reduced PDA cell synthesis of MCP-1, TNF-alpha, interleukin 
      (IL)-1beta and Cox-2. At 24 h, Tq almost completely abolished the expression of 
      these cytokines, whereas TSA had a less dramatic effect. Tq, but not TSA, 
      significantly and dose-dependently reduced the intrinsic activity of the MCP-1 
      promoter. Tq also inhibited the constitutive and TNF-alpha-mediated activation of 
      NF-kappaB in PDA cells and reduced the transport of NF-kappaB from the cytosol to 
      the nucleus. CONCLUSIONS: Our data demonstrate previously undescribed 
      anti-inflammatory activities of Tq in PDA cells, which are paralleled by 
      inhibition of NF-kappaB. Tq as a novel inhibitor of proinflammatory pathways 
      provides a promising strategy that combines anti-inflammatory and proapoptotic 
      modes of action.
FAU - Chehl, Navdeep
AU  - Chehl N
AD  - Department of Surgery, Thomas Jefferson University, Philadelphia, PA 19107, USA.
FAU - Chipitsyna, Galina
AU  - Chipitsyna G
FAU - Gong, Qiaoke
AU  - Gong Q
FAU - Yeo, Charles J
AU  - Yeo CJ
FAU - Arafat, Hwyda A
AU  - Arafat HA
LA  - eng
PT  - Journal Article
PL  - England
TA  - HPB (Oxford)
JT  - HPB : the official journal of the International Hepato Pancreato Biliary 
      Association
JID - 100900921
PMC - PMC2742606
OTO - NOTNLM
OT  - Nigella sative
OT  - inflammation
OT  - pancreatic cancer
OT  - thymoquinone
EDAT- 2009/09/22 06:00
MHDA- 2009/09/22 06:01
PMCR- 2010/08/01
CRDT- 2009/09/22 06:00
PHST- 2008/11/13 00:00 [received]
PHST- 2009/03/17 00:00 [accepted]
PHST- 2009/09/22 06:00 [entrez]
PHST- 2009/09/22 06:00 [pubmed]
PHST- 2009/09/22 06:01 [medline]
PHST- 2010/08/01 00:00 [pmc-release]
AID - S1365-182X(15)30188-X [pii]
AID - 10.1111/j.1477-2574.2009.00059.x [doi]
PST - ppublish
SO  - HPB (Oxford). 2009 Aug;11(5):373-81. doi: 10.1111/j.1477-2574.2009.00059.x.