Parthenolide Inhibits Activation of Signal Transducers and Activators of Transcription (STATs) Induced by Cytokines of the IL-6 Family

Sobota, Radoslaw M.; Szwed, Marcin; Kasza, Aneta; Bugno, Marcin; Kordula, Tomasz

doi:10.1006/bbrc.1999.1948

Cited by 126 publications

(105 citation statements)

References 18 publications

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“…PT is an effective inhibitor of IL-6-type cytokines, which activate the phosphorylation of STAT3 on Tyr 705. PT has been demonstrated to prevent the activity of IL-6-type cytokines by inhibiting the phosphorylation of STAT3 on Tyr 705 (32,33), indicating that PT, as an inhibitor of IL-6, is able to provide protection from carcinogenesis in experimental CAC models. Although the present study did not demonstrate the role of PT in regulating and suppressing carcinogenesis via the IL-6/STAT3 pathway, additional important insights into the mechanism were obtained.…”

Section: Discussionmentioning

confidence: 99%

Parthenolide induces apoptosis in colitis-associated colon cancer, inhibiting NF-κB signaling

et al. 2015

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Abstract. Recently, the nuclear factor (NF)-κB inhibitor parthenolide (PT) was identified as a promising anticancer agent for the promotion of cancer cell apoptosis. Additionally, our previous study demonstrated that PT administration suppresses tumor growth in a xenograft model of colorectal cancer cells via regulation of the B-cell lymphoma-2 (Bcl-2) family. However, the role of PT in the development of colitis-associated colon cancer (CAC) is poorly understood. Therefore, the aim of the present study was to investigate the effects of PT administration on CAC using a murine model. Azoxymethane (AOM) and dextran sulfate sodium (DSS) were administered to induce experimental CAC in the following three groups of treated mice: i) AOM and DSS plus vehicle; ii) AOM, DSS and 2 mg/kg PT; and iii) AOM, DSS and 4 mg/kg PT. It was demonstrated that the histological acuteness of AOM/DSS-induced CAC was significantly reduced following the administration of PT, resulting in decreased NF-κB p65 expression levels via a blockade of phosphorylation and subsequent degradation of inhibitor of κB-α (IκBα). Furthermore, PT administration appeared to enhance the process of carcinogenesis via the downregulation of the antiapoptotic proteins Bcl-2 and Bcl-extra large, mediated by inhibition of NF-κB activation. Apoptosis and caspase-3 expression were markedly increased in the PT-treated group. These findings indicate that PT inhibits IκBα phosphorylation and NF-κB activation, resulting in the initiation of apoptosis and the eventual suppression of CAC development. The beneficial effects of PT treatment observed in the experimental CAC model indicate the potential chemopreventive and therapeutic role of PT in CAC.

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Section: Discussionmentioning

confidence: 99%

Parthenolide induces apoptosis in colitis-associated colon cancer, inhibiting NF-κB signaling

et al. 2015

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“…Sobota et al showed that parthenolide is also an effective inhibitor of these inflammatory cytokines IL-1 and IL-6. It hinders IL-6 induced gene expression by blocking STAT3 phosphorylation on Tyr705 [36]. PTL inhibits LPS-induced COX-2 protein, mRNA expressions in alveolar macrophage cells, production of IL-1β and prostaglandin E2 (PGE2) and activation of the Akt/mTOR [37,38].…”

Section: Parthenolide and Statmentioning

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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“…Inflammation is a pathophysiological response of mammalian tissues to a variety of hostile agents including infectious organisms, toxic chemical substances, physical injury or tumor growth leading to local accumulation of plasmic fluid and blood cells (Sobota et al, 2000). Although a defense mechanism, the complex events and mediators involved in the inflammatory reaction can induce, maintain and aggravate many disorders.…”

Section: Introductionmentioning

confidence: 99%

Anti-inflammatory and analgesic activity of the methanol extract of Malva parviflora Linn (Malvaceae) in rats

Afolayan¹,

Aboyade²,

Adedapo³

et al. 2010

Afr. J. Biotechnol.

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Malva parviflora Linn Malvaceae is a medicinal plant used for the treatment of wounds and other related ailments by the Xhosa people of South Africa. The anti-inflammatory activity of the stem extract of this plant was assessed using carrageenan-induced paw oedema and histamine-induced paw oedema. The analgesic effect was determined using the acetic acid writhing method as well as formalin test. The extract at 100 and 200 mgkg -1 body weight reduced significantly, the formation of oedema induced by carrageenan and histamine. In the acetic acid-induced writhing model, the extract showed a good analgesic effect characterized by reduction in the number of writhes when compared to the control. The extract caused dose-dependent decrease of licking time and licking frequency in rats injected with 2.5% formalin, signifying its analgesic effect. These results were also comparable to those of indomethacin, the reference drug used in this study. Since the plant extract reduced significantly the formation of oedema induced by carrageenan and histamine as well as reduced the number of writhes in acetic acidinduced writhing models and dose-dependent decrease of licking time and licking frequency in rats injected with 2.5% formalin, it is concluded that the use of M. parviflora for the treatment of inflammed purulent wounds, swellings, bruises and broken limbs may have been justified.

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Parthenolide Inhibits Activation of Signal Transducers and Activators of Transcription (STATs) Induced by Cytokines of the IL-6 Family

Cited by 126 publications

References 18 publications

Parthenolide induces apoptosis in colitis-associated colon cancer, inhibiting NF-κB signaling

Parthenolide induces apoptosis in colitis-associated colon cancer, inhibiting NF-κB signaling

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

Anti-inflammatory and analgesic activity of the methanol extract of Malva parviflora Linn (Malvaceae) in rats

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