Suppression of 5-lipoxygenase gene is involved in triptolide-induced apoptosis in pancreatic tumor cell lines

Pancreatic adenocarcinoma is characterized by a poor prognosis and lack of response to conventional therapy. The purpose of this study was to investigate the effects of triptolide (TL) on proliferation and apoptosis of pancreatic cancer cells in vitro. We found that TL induced prominent growth inhib...

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Vydáno v:Biochimica et biophysica acta Ročník 1770; číslo 7; s. 1021 - 1027
Hlavní autoři: Zhou, G.X., Ding, X.L., Huang, J.F., Zhang, H., Wu, S.B.
Médium: Journal Article
Jazyk:angličtina
Vydáno: Netherlands Elsevier B.V 01.07.2007
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ISSN:0304-4165, 0006-3002, 1872-8006
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Abstract Pancreatic adenocarcinoma is characterized by a poor prognosis and lack of response to conventional therapy. The purpose of this study was to investigate the effects of triptolide (TL) on proliferation and apoptosis of pancreatic cancer cells in vitro. We found that TL induced prominent growth inhibition and apoptosis in human pancreatic cell lines. In addition, TL treatment significantly down-regulated 5-lipoxygenase (5-LOX) expression, as well as downstream leukotriene B4 (LTB4) production, in these cell lines. Furthermore, overexpression of 5-LOX in SW1990 cell lines or exogenous LTB4 made them more resistant to TL-induced apoptosis, which was correlated with increased Bcl-2 expression. Taken together, these findings suggest that inhibition of the 5-LOX pathway of arachidonic acid metabolism is associated with the anti-proliferation activity of TL. We also provide evidence that TL has clinical therapeutic value for patients with pancreatic cancer.
AbstractList Pancreatic adenocarcinoma is characterized by a poor prognosis and lack of response to conventional therapy. The purpose of this study was to investigate the effects of triptolide (TL) on proliferation and apoptosis of pancreatic cancer cells in vitro. We found that TL induced prominent growth inhibition and apoptosis in human pancreatic cell lines. In addition, TL treatment significantly down-regulated 5-lipoxygenase (5-LOX) expression, as well as downstream leukotriene B4 (LTB4) production, in these cell lines. Furthermore, overexpression of 5-LOX in SW1990 cell lines or exogenous LTB4 made them more resistant to TL-induced apoptosis, which was correlated with increased Bcl-2 expression. Taken together, these findings suggest that inhibition of the 5-LOX pathway of arachidonic acid metabolism is associated with the anti-proliferation activity of TL. We also provide evidence that TL has clinical therapeutic value for patients with pancreatic cancer.
Pancreatic adenocarcinoma is characterized by a poor prognosis and lack of response to conventional therapy. The purpose of this study was to investigate the effects of triptolide (TL) on proliferation and apoptosis of pancreatic cancer cells in vitro. We found that TL induced prominent growth inhibition and apoptosis in human pancreatic cell lines. In addition, TL treatment significantly down-regulated 5-lipoxygenase (5-LOX) expression, as well as downstream leukotriene B4 (LTB4) production, in these cell lines. Furthermore, overexpression of 5-LOX in SW1990 cell lines or exogenous LTB4 made them more resistant to TL-induced apoptosis, which was correlated with increased Bcl-2 expression. Taken together, these findings suggest that inhibition of the 5-LOX pathway of arachidonic acid metabolism is associated with the anti-proliferation activity of TL. We also provide evidence that TL has clinical therapeutic value for patients with pancreatic cancer.Pancreatic adenocarcinoma is characterized by a poor prognosis and lack of response to conventional therapy. The purpose of this study was to investigate the effects of triptolide (TL) on proliferation and apoptosis of pancreatic cancer cells in vitro. We found that TL induced prominent growth inhibition and apoptosis in human pancreatic cell lines. In addition, TL treatment significantly down-regulated 5-lipoxygenase (5-LOX) expression, as well as downstream leukotriene B4 (LTB4) production, in these cell lines. Furthermore, overexpression of 5-LOX in SW1990 cell lines or exogenous LTB4 made them more resistant to TL-induced apoptosis, which was correlated with increased Bcl-2 expression. Taken together, these findings suggest that inhibition of the 5-LOX pathway of arachidonic acid metabolism is associated with the anti-proliferation activity of TL. We also provide evidence that TL has clinical therapeutic value for patients with pancreatic cancer.
Author Huang, J.F.
Wu, S.B.
Zhang, H.
Ding, X.L.
Zhou, G.X.
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Issue 7
Keywords Pancreatic tumor
Bcl-2
Triptolide
TL
LTB4
5-lipoxygenase
5-LOX
Caspase-3
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Snippet Pancreatic adenocarcinoma is characterized by a poor prognosis and lack of response to conventional therapy. The purpose of this study was to investigate the...
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SubjectTerms 5-lipoxygenase
Apoptosis - drug effects
Arachidonate 5-Lipoxygenase - metabolism
Bcl-2
Blotting, Western
Caspase 3 - metabolism
Caspase-3
Cell Line, Tumor
Cell Proliferation - drug effects
Diterpenes - pharmacology
DNA Primers
Enzyme-Linked Immunosorbent Assay
Epoxy Compounds - pharmacology
Flow Cytometry
Gene Expression Regulation - drug effects
Humans
In Situ Nick-End Labeling
Leukotriene B4 - metabolism
Luciferases
Pancreas - cytology
Pancreas - drug effects
Pancreatic tumor
Phenanthrenes - pharmacology
Proto-Oncogene Proteins c-bcl-2 - metabolism
Reverse Transcriptase Polymerase Chain Reaction
Triptolide
Title Suppression of 5-lipoxygenase gene is involved in triptolide-induced apoptosis in pancreatic tumor cell lines
URI https://dx.doi.org/10.1016/j.bbagen.2007.03.002
https://www.ncbi.nlm.nih.gov/pubmed/17434678
https://www.proquest.com/docview/70478679
Volume 1770
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