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Anti-inflammatory effects of the Nigella sativa seed extract, thymoquinone, in pancreatic cancer cells.

ABSTRACT: 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.

SUBMITTER: Chehl N

PROVIDER: S-EPMC2742606 | biostudies-literature | 2009 Aug

REPOSITORIES: biostudies-literature

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Anti-inflammatory effects of the Nigella sativa seed extract, thymoquinone, in pancreatic cancer cells.

Chehl Navdeep N Chipitsyna Galina G Gong Qiaoke Q Yeo Charles J CJ Arafat Hwyda A HA

HPB : the official journal of the International Hepato Pancreato Biliary Association 20090801 5

<h4>Background</h4>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 deacety ...[more]

PMID: 19768141

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Project description:Nigella sativa L. (Ranunculaceae), commonly referred to as black seeds or black cumin, is used in popular medicine (herbal) all over the world for the treatment and prevention of several diseases, including diabetes. This study aims to investigate the inhibitory effect of N. sativa extracts and fractions against the activities of intestinal α-glucosidase and pancreatic α-amylase in vitro, and to explain the inhibitory effect of these fractions against these enzymes by identifying their active compounds responsible for this effect and determine their modes of inhibition. To do so, N. sativa hexane and acetone extracts were prepared and analyzed by GC-MS and HPLC-DAD, respectively. The hexane extract was further fractioned into eight different fractions, while the acetone extract generated eleven fractions. The extracts as well as the resulting fractions were characterized and evaluated for their potential in vitro antidiabetic activity using intestinal α-glucosidase and pancreatic α-amylase inhibitory assays in vitro. Hexane extract and fractions were less active than acetone extract and fractions. In the case of intestinal α-glucosidase activity, the acetone fraction SA3 had a high inhibitory effect on intestinal α-glucosidase activity with 72.26 ± 1.42%, comparable to the effect of acarbose (70.90 ± 1.12%). For the pancreatic α-amylase enzymatic inhibitory assay, the acetone fractions showed an inhibitory capacity close to that for acarbose. In particular, the SA2 fraction had an inhibitory effect of 67.70 ± 0.58% and was rich in apigenin and gallic acid. From these fractions, apigenin, (-)-catechin, and gallic acid were further characterized for their inhibitory actions. IC50 and inhibition mode were determined by analyzing enzyme kinetic parameters and by molecular modeling. Interestingly, (-)-catechin showed a possible synergistic effect with acarbose toward α-glucosidase enzyme inhibition, whereas apigenin showed an additive effect with acarbose toward α-amylase enzymatic inhibition. Furthermore, we studied the toxicity of N. sativa hexane and acetone extracts as well as that of acetone fractions. The result of acute toxicity evaluation demonstrated that N. sativa extracts were nontoxic up to a concentration of 10 g/kg, except for fraction SA3. Taken together, these results indicate that N. sativa extracts and/or derived compounds could constitute promising nutraceuticals for the prevention and treatment of type 2 diabetes mellitus.

Dataset Information

Anti-inflammatory effects of the Nigella sativa seed extract, thymoquinone, in pancreatic cancer cells.

Publications

Anti-inflammatory effects of the Nigella sativa seed extract, thymoquinone, in pancreatic cancer cells.

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