Inhibition by parthenolide of phorbol ester-induced transcriptional activation of inducible nitric oxide synthase gene in a human monocyte cell line THP-1

Fukuda, Kazunori; Hibiya, Yuko; Mutoh, Michihiro; Ohno, Yasushi; Yamashita, Kazuya; Akao, Seigou; Fujiwara, Hisayoshi

doi:10.1016/s0006-2952(00)00340-3

Cited by 36 publications

(21 citation statements)

References 15 publications

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“…26) Studies have shown that parthenolide effectively inhibited 12-O-tetradecanoylphorbol-13-acetate-mediated induction of iNOS expression and NO production in THP-1 cells. 27) Curcumin, a natural flavonoid found in Curcuma species, inhibited phorbol ester-mediated induction of COX-2 as well as LPS-stimulated iNOS expression. 26) Capsaicin, a major ingredient of hot pepper, markedly inhibited PGE 2 release by inhibiting the catalytic activity of the COX-2 enzyme.…”

Section: Discussionmentioning

confidence: 99%

Tetrandrine Inhibits Proinflammatory Cytokines, iNOS and COX-2 Expression in Human Monocytic Cells

2007

Biological & Pharmaceutical Bulletin

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Section: Discussionmentioning

confidence: 99%

Tetrandrine Inhibits Proinflammatory Cytokines, iNOS and COX-2 Expression in Human Monocytic Cells

2007

Biological & Pharmaceutical Bulletin

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“…Several anti-LPS or anti-cytokine clinical trials have been conducted, but none has so far been successful. Parthenolide (PTL), a sesquiterpene lactone (SL) originally purified from the shoots of feverfew (Tanacetum parthenium), has shown potent anti-cancer and anti-inflammatory activities [9]. Some observations revealed that the anti-inflammatory property of PTL in THP-1 cells, a human leukemia monocytic cell line, is partly due to its inhibition of inducible nitric oxide synthase (iNOS) promoter activation [9].…”

Section: Introductionmentioning

confidence: 99%

“…Parthenolide (PTL), a sesquiterpene lactone (SL) originally purified from the shoots of feverfew (Tanacetum parthenium), has shown potent anti-cancer and anti-inflammatory activities [9]. Some observations revealed that the anti-inflammatory property of PTL in THP-1 cells, a human leukemia monocytic cell line, is partly due to its inhibition of inducible nitric oxide synthase (iNOS) promoter activation [9]. What's more, there is a study showing that PTL can attenuate NF-κB activation after an LPS challenge in rat myocardium [10].…”

Section: Introductionmentioning

confidence: 99%

Parthenolide inhibits LPS-induced inflammatory cytokines through the toll-like receptor 4 signal pathway in THP-1 cells

Li¹,

Gao²,

Wu³

et al. 2015

ABBS

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Parthenolide (PTL) shows potent anti-inflammatory and anti-cancer activities. In the present study, the molecular mechanisms of PTL's activities were explored in lipopolysaccharide (LPS)-induced human leukemia monocytic THP-1 cells and human primary monocytes. The 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium salt (MTS) assay was used to analyze the effect of PTL on THP-1 cell viability. Enzyme-linked immunosorbent assay was used to determine the effect of PTL on LPS-induced inflammatory cytokine secretion. Flow cytometry and quantitative real-time polymerase chain reaction were used to assess the effect of PTL on LPSinduced toll-like receptor 4 (TLR4) expression. Phosphorylation levels of signaling molecules were determined by western blot analysis. Results showed that PTL <12.5 μM did not significantly affect THP-1 cells viability. LPS treatment led to a marked up-regulation of interleukin (IL)-6, IL-1β, IL-8, IL-12p40, tumor necrosis factor-α, IL-18, and NO in THP-1 cells. However, PTL inhibited the expression of these cytokines in a dose-dependent manner, with IC 50 values of 1.091-2.620 μM. PTL blocked TLR4 expression with an IC 50 value of 1.373 μM as determined by the flow cytometry analysis, and this blocking effect was verified at both protein and mRNA levels. Up-regulation of phosphorylation levels of extracellular signal-regulated kinase 1/2, Jun N-terminal kinase, p38, nuclear factor κB (NF-κB) p65, and IκBα and up-regulation of expressions of other molecules (inducible nitric oxide synthase, TLR4, and TNF receptor-associated factor 6) induced by LPS were abolished by PTL in a dose-dependent manner. The anti-inflammatory mechanisms of PTL operate partly through the TLR4-mediated mitogen-activated protein kinase and NF-κB signaling pathways. Therefore, TLR4 may be a new target for anti-inflammation therapies.

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“…Parthenolide has been reported to inhibit NF-B by targeting the IB kinase complex (7). Parthenolide also exerts an anti-inflammatory activity by inhibiting the expression of inducible cyclooxygenase, proinflammatory cytokines (8), and inducible nitric-oxide synthase (9). In contrast, the cytotoxic and antitumor effects of sesquiterpene lactones have not been well studied because of their low potency.…”

mentioning

confidence: 99%

Oxidative Stress-mediated Apoptosis

Wen

You

Lee

et al. 2002

Journal of Biological Chemistry

290

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The sesquiterpene lactone parthenolide, the principal active component in medicinal plants, has been used conventionally to treat migraines, inflammation, and tumors. However, the antitumor effects of parthenolide and the mechanism(s) involved are poorly understood. We found that parthenolide effectively inhibits hepatoma cell growth in a tumor cell-specific manner and triggers apoptosis of hepatoma cells. Parthenolide triggered apoptosis in invasive sarcomatoid hepatocellular carcinoma cells (SH-J1) as well as in other ordinary hepatoma cells at 5-10 M concentrations and arrested the cell growth (at G 2 /M) at sublethal concentrations (1-3 M). During parthenolide-induced apoptosis, depletion of glutathione, generation of reactive oxygen species, reduction of mitochondrial transmembrane potential, activation of caspases (caspases-7, -8, and -9), overexpression of GADD153 (an oxidative stress or anticancer agent inducible gene), and subsequent apoptotic cell death was observed. This induced apoptosis could be effectively inhibited or abrogated by an antioxidant N-acetyl-L-cysteine, whereas L-buthionine-(S, R)-sulfoximine enhanced it. Furthermore, stable overexpression of GADD153 sensitized the cells to apoptosis induced by parthenolide, and this susceptibility could be reversed by transfection with an antisense to GADD153. Parthenolide did not alter the expression of Bcl-2 or Bcl-X L proteins during apoptosis in hepatoma cells. Oxidative stress may contribute to parthenolide-induced apoptosis and to GADD153 overexpression in a glutathione-sensitive manner. The sensitivity of tumor cells to parthenolide appears to result from the low expression level of the multifunctional detoxification enzyme glutathione S-transferase . Finally, parthenolide and its derivatives may be useful chemotherapeutic agents to treat these invasive cancers.Sesquiterpene lactones are isolated from extracts of Mexican-Indian medicinal plants and have been widely used in indigenous medical practices, including treatment of migraines (1, 2), inflammation (3), and tumors (4, 5). Parthenolide, the major sesquiterpene lactone found in medicinal plants such as feverfew (Tanacetum parthenium), is known to inhibit interleukin 1-and tumor necrosis factor ␣-mediated NF-B activation, which is responsible for its anti-inflammatory activity (6, 7). Parthenolide has been reported to inhibit NF-B by targeting the IB kinase complex (7). Parthenolide also exerts an anti-inflammatory activity by inhibiting the expression of inducible cyclooxygenase, proinflammatory cytokines (8), and inducible nitric-oxide synthase (9). In contrast, the cytotoxic and antitumor effects of sesquiterpene lactones have not been well studied because of their low potency. Recently it has been reported that parthenolide inhibits the in vitro growth of tumor cells in a cytostatic fashion, and it has been proposed that if their selectively cytotoxic or cytostatic actions against tumor cells can be established, sesquiterpene lactones may represent a new class of cancer chemotherapeuti...

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Inhibition by parthenolide of phorbol ester-induced transcriptional activation of inducible nitric oxide synthase gene in a human monocyte cell line THP-1

Cited by 36 publications

References 15 publications

Tetrandrine Inhibits Proinflammatory Cytokines, iNOS and COX-2 Expression in Human Monocytic Cells

Tetrandrine Inhibits Proinflammatory Cytokines, iNOS and COX-2 Expression in Human Monocytic Cells

Parthenolide inhibits LPS-induced inflammatory cytokines through the toll-like receptor 4 signal pathway in THP-1 cells

Oxidative Stress-mediated Apoptosis

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