Triptolide suppresses 5-lipoxygenase metabolic pathway and induces apoptosis in pancreatic tumor cell lines

Xiao Ling Ding, Guo Xiong Zhou, Xiao Rong Zhou, Xiao Ying Wang

Research output: Contribution to journalArticle

Abstract

AIM: To investigate the effects and the mechanism of triptolide (TL) on proliferation and apoptosis of pancreatic cancer in vitro. METHODS: Pancreatic tumor cell lines PANC-1, ASPC-1 and SW1990 were treated with different concentrations of TL for 24 h and then, cell death was determined by Typan Blue Staining. Annexin V/PI double staining was performed to evaluate TL-induced apoptosis using flow cytometry. The expression of 5-lipoxygenase (5-LOX) and concentration of its downstream product LTB4 were determined by real time PCR, Western blot and ELISA. 5-LOX cDNA stable transfected SW1990 cells were established successfully. After treatment with TL, it was examined for overexpression of 5-LOX on TL-induced apoptosis. RESULTS: TL induced prominent growth inhibition and apoptosis in human pancreatic cancer cell lines. After treatment at 50 μg/L, the cell viability was 70.5% ± 6.8%, 61.2% ± 5.6% and 52.8% ± 5.3% of PANC-1, ASPC-1 and SW1990, respectively, which were significantly decreased compared with control group (P < 0.05). The apoptosis at 12 h evaluated by AnnexinV positive cells increased in TL-treated group compared with control group (24.2 ± 3.23 vs 9.5 ± 2.18, P < 0.05). TL significantly down-regulated 5-LOX expression in these cell lines and decreased LTB4 concentration in supernatant (P < 0.01, compared with control group). Furthermore, overexpression of 5-LOX in SW1990 cells made them more resistant to TL induced apoptosis, significantly inhibited the TL mediated cell death and apoptosis (P < 0.01 or 0.05, compared with control group). CONCLUSION: Inhibition of 5-LOX pathway of arachidonic acid metabolism is associated with TL's anti-proliferation and pro-apoptotic activity. It also provides evidence that TL has clinic therapeutic value for patients with pancreatic cancer.

Original languageEnglish (US)
Pages (from-to)3835-3839
Number of pages5
JournalWorld Chinese Journal of Digestology
Volume16
Issue number34
StatePublished - Dec 1 2008

Keywords

  • 5-Lipoxygenase
  • Pancreatic cancer
  • Triptolide

ASJC Scopus subject areas

  • Gastroenterology

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