Inhibition of 5-lipoxygenase and cyclo-oxygenase in leukocytes by feverfew

Sumner, Helen L.; Salan, Ümit; Knight, David W.; Hoult, J.R.S.

doi:10.1016/0006-2952(92)90308-6

Cited by 84 publications

(36 citation statements)

References 23 publications

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“…Parthenolide has been reported to have microtubuleinterfering properties (31) that induce apoptotic cell death by multiple pathways, including oxidative stress, endoplasmic reticulum stress, intracellular thiol depletion, caspase activation, and mitochondrial dysfunction (15,17,18), inhibit 5-lipoxygenase and cyclooxygenase (32) and sensitize cancer cells to chemotherapeutic drugs such as paclitaxel and docetaxel (33,34). Despite widely documented anti-cancer activity and the absence of major adverse effects, clinical development of parthenolide is hampered by its poor water solubility, (35) thus limiting its potential as a promising clinical agent.…”

Section: Discussionmentioning

confidence: 99%

Radio-sensitization of the murine osteosarcoma cell line LM8 with parthenolide, a natural inhibitor of NF-κB

et al. 2011

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Abstract. Nuclear factor (NF)-κB has been shown to be associated with cancer resistance to radiotherapy (RT), and is constitutively active in the murine osteosarcoma cell line, LM8. Parthenolide has been reported to show antitumor activity through inhibition of the NF-κB pathway. In this study, we investigated the radio-sensitizing activity of parthenolide. We established Luc-LM8, a stable transfectant reporter construct of NF-κB transcriptional activity into LM8. Luc-LM8 maintained the malignancy observed with LM8. In vitro, Luc-LM8 cells were cultured with or without parthenolide treatment, irradiated, and subjected to cell viability and apoptosis assays. In vivo, to investigate whether parthenolide enhances radio-sensitivity of tumors, a tumor growth assay was conducted. Parthenolide enhanced the growth inhibitory effect of RT and induced the apoptosis of Luc-LM8 cells with RT in vitro. The in vivo tumor growth was significantly suppressed in the mice treated with parthenolide and RT. The present study suggests that parthenolide sensitizes Luc-LM8 cells to irradiation. Thus, parthenolide is a potential candidate for use as a potent radio-sensitizing drug for use in cancer RT.

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Section: Discussionmentioning

confidence: 99%

Radio-sensitization of the murine osteosarcoma cell line LM8 with parthenolide, a natural inhibitor of NF-κB

et al. 2011

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“…Among the sesquiterpene lactones, helenalin 93 from Arnica Montana [62] and parthenolide 92 from Tanacetum parthenium [176] interfere with 5-LO product synthesis. These agents usually act by forming covalent bonds via an a-methylene-g-lactone group with free thiol groups of cysteine residues in their target enzyme.…”

Section: Sesquiterpenesmentioning

confidence: 99%

Inhibition of 5-Lipoxygenase Product Synthesis by Natural Compounds of Plant Origin

Werz¹

2007

Planta Med

153

135

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The biosynthesis of leukotrienes (LTs) is initiated by the transformation of free arachidonic acid to LTA 4 by 5-lipoxygenase (5-LO). Subsequent enzymatic conversion of LTA 4 yields LTB 4 and the cysteinyl-LTs C 4 , D 4 and E 4 . LTs have prominent functions in pathophysiology and are connected to numerous disorders including bronchial asthma, allergic rhinitis, inflammatory bowel and skin diseases, rheumatoid arthritis, cancer, osteoporosis and cardiovascular diseases. Pharmacological and genetic interruption of the 5-LO pathway or blockade of LT receptors, serving as means for intervention with LTs, may be of therapeutic value for certain related disorders. Natural or plant-derived substances were among the first 5-LO inhibitors identified in the early 1980 s. To date, a huge number of diverse plant-derived compounds have been reported to interfere with 5-LO product synthesis. However, many investigations have addressed the efficacy of a given compound solely in cellular test systems and analysis of direct interference with 5-LO has been neglected. In the first part of this review, the biology and molecular pharmacology of the 5-LO pathway is summarized in order to understand its overall regulation and complexity as well as to comprehend the possible points of attack of compounds that eventually lead to inhibition of 5-LO product formation in intact cells. In the second part, natural compounds that interfere with 5-LO product formation are compiled and grouped into structural classes, and the underlying molecular mechanisms and structureactivity relationships are discussed.

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“…PTL inhibited histamine release from rat peritoneal mast cells [26]. Further studies revealed that it inhibits inflammatory mediators including activity and expression of cyclo-oxygenase (COX) specifically COX-2, which also enhances cancer stem-like cells' characteristics such as higher colony formation efficiency and over expression of stemness-associated genes [27][28][29]. The compound was found to inhibit activation of transcription factor NFκB by both at the transcriptional level and by direct inhibition of associated kinases (IKK-β) [30,31].…”

Section: Parthenolide and Statmentioning

confidence: 99%

“…References Cell Proliferation/ Apoptosis associated Molecules References NFκB [14], [30], [31], [35], [43], [48], [90] NFκB [17], [18], [21], [52], [54], [64], [78][79], [90] IKK-β [30][31][32], [48] [ERK/MEK/MAPK/ELK1] [14], [37], [48], [51] iNOS [39] β1-arrestin, Csk, FAK, FGFR2, PKC [51] STAT1/STAT3 [36], [51], [83][84][85][86][87][88] STAT1/STAT3 [36], [51], [55][56], [83][84][85][86][87][88] Cyclooxygenase (COX) [27][28][29], [37] JNK [42], [43], …”

Section: Inflammatory Moleculesmentioning

confidence: 99%

Anti-inflammatory and Anti-tumor Activities of Parthenolide: An Update

Dey¹,

Sarkar²,

Giri³

2016

J Chem Biol Ther

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Parthenolide (PTL), the secondary metabolite of feverfew plant (Tanaceum parthenium), has been used in various medical purposes globally. Inflammation represents a physiological response to injury and helps to restore tissue homeostasis. Inflammation and cancer both are associated with genotoxicity, invasion, metastasis, and abnormal tissue repair mechanisms. PTL inhibit major cellular inflammatory and proliferation pathways like NFκB, STAT3, and MAPK along with the activity and expression of several inflammatory mediators including COX. NFκB pathway plays a key role in controlling cell cycle progression and apoptosis together with metastasis and cancer of various types. Elevated NFκB, Wnt/β-catenin pathways are crucial factors of tumorogenesis. PTL inhibits NFκB and Wnt/β-catenin pathways, and thereby promotes apoptosis and suppresses cell proliferation. Experimental data showed that PTL protects normal cells from apoptosis; whereas in cancer cells it induces apoptotic cell death. Hence, parthenolide could be useful in controlling inflammatory diseases alone or together with tumorogenesis due to its evident anticancer potency and anti-inflammatory nature.

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Inhibition of 5-lipoxygenase and cyclo-oxygenase in leukocytes by feverfew

Cited by 84 publications

References 23 publications

Radio-sensitization of the murine osteosarcoma cell line LM8 with parthenolide, a natural inhibitor of NF-κB

Radio-sensitization of the murine osteosarcoma cell line LM8 with parthenolide, a natural inhibitor of NF-κB

Inhibition of 5-Lipoxygenase Product Synthesis by Natural Compounds of Plant Origin

Anti-inflammatory and Anti-tumor Activities of Parthenolide: An Update

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