Emodin has a cytotoxic activity against human multiple myeloma as a Janus-activated kinase 2 inhibitor

Muto, Akihiro; Hori, Mayumi; Sasaki, Yoshi K.; Saitoh, Akari; Yasuda, Iho; Maekawa, Tadahito; Uchida, Tomoe; Asakura, Keiko; Nakazato, Tomonori; Kaneda, Toshio; Kizaki, Masahiro; Ikeda, Yasuo; Yoshida, Tadashi

doi:10.1158/1535-7163.mct-06-0605

Cited by 118 publications

(82 citation statements)

References 52 publications

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“…It also promotes the apoptosis of human breast cancer BCap-37 cells . Some studies have also reported the effect of emodin on cell death in human prostate, lung, liver, cervical and blood cancer cells (Cha et al, 2005;Su et al, 2005;Jing et al, 2006;Fu et al, 2007;Muto et al, 2007). In this study, compound 5 (emodin) and ampicillin acted jointly against P. aeruginosa more effectively than either of them did alone, suggesting that compound 5 enhanced the activity of ampicillin against P. aeruginosa.…”

Section: Discussionsupporting

confidence: 55%

Screening for novel quorum-sensing inhibitors to interfere with the formation of Pseudomonas aeruginosa biofilm

Ding

Yin

et al. 2011

Journal of Medical Microbiology

126

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The objective of this study was to screen for novel quorum-sensing inhibitors (QSIs) from traditional Chinese medicines (TCMs) that inhibit bacterial biofilm formation. Six of 46 active components found in TCMs were identified as putative QSIs based on molecular docking studies. Of these, three compounds inhibited biofilm formation by Pseudomonas aeruginosa and Stenotrophomonas maltophilia at a concentration of 200 mM. A fourth compound (emodin) significantly inhibited biofilm formation at 20 mM and induced proteolysis of the quorum-sensing signal receptor TraR in Escherichia coli at a concentration of 3-30 mM. Emodin also increased the activity of ampicillin against P. aeruginosa. Therefore, emodin might be suitable for development into an antivirulence and antibacterial agent. INTRODUCTIONPseudomonas aeruginosa, an opportunistic human pathogen, may cause acute infections in hospitalized patients, can be isolated from the environment, particularly from soil and water, and it regularly contaminates medical devices (Stover et al., 2000). It is also the predominant cause of chronic lung infection in cystic fibrosis patients (Frederiksen et al., 1997) and has recently been recognized as one of the main causes of chronic wound infections (Gjødsbøl et al., 2006). P. aeruginosa can infect patients by producing a wide range of virulence factors, the expression levels of which are tightly regulated. Key to this regulation is cell density-dependent cell-to-cell signalling, which is termed quorum sensing (QS) (Rumbaugh et al., 2000). As in many other bacteria, QS controls secretion of virulence factors (Mittal et al., 2006), biofilm formation (Waters et al., 2008) and the exchange of DNA (Fuqua & Winans, 1996) in P. aeruginosa. The biofilm mode of growth is recognized as an important bacterial trait that is relevant to infections (Costerton et al., 1994). Many infections involve the formation of bacterial biofilms, which are bacterial communities that settle and proliferate on surfaces and are covered by exopolymers (Lewis, 2007). Once established, biofilms are difficult to eradicate and become a source of secondary infection (Jones et al., 2009). Moreover, bacteria embedded in biofilms are more tolerant than planktonic cells of antibiotics (Donlan & Costerton, 2002;Drenkard, 2003). The dose of antibiotics needed in this situation will often exceed the highest deliverable dose, which makes efficient treatment impossible.QS, as a regulatory mechanism, enables bacteria to make collective decisions with respect to the expression of a specific set of genes that involve the production, release and subsequent detection of chemical signalling molecules, such as N-acylhomoserine lactones (AHLs) that are commonly used by Gram-negative bacteria. When the concentration of AHLs reaches a certain threshold level, binding to a receptor molecule (for example, LuxR) is promoted and the activated LuxR-AHL complex forms dimers or polymers, which, in turn, act as transcriptional regulators of target genes in the QS regulon (Parsek & Greenbe...

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Section: Discussionsupporting

confidence: 55%

Screening for novel quorum-sensing inhibitors to interfere with the formation of Pseudomonas aeruginosa biofilm

Ding

Yin

et al. 2011

Journal of Medical Microbiology

126

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“…This EM has been used as a traditional oriental medicine for the treatment of skin burn, infection, gallstone, hepatitis, inflammation, and osteomyelitis. Moreover, this is a safe agent even in long exposure in mice (Muto et al, 2007). Hatano et al (1999) reported that EM, aloe-emodin, and the others, showed strong antibacterial activity against MRSA.…”

Section: Discussionmentioning

confidence: 94%

Synergistic effect of emodin in combination with ampicillin or oxacillin against methicillin-resistantStaphylococcus aureus

Lee

Kang

Choi

et al. 2010

Pharmaceutical Biology

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“…Emodin is a potent inhibitor of casein kinase 2 (CK2), which regulates JAK/STAT signaling (55). Furthermore, emodin has been shown to directly inhibit JAK activity (56). Emodin has also been reported to be an agonist for PPAR␥ (51).…”

Section: Discussionmentioning

confidence: 99%

Emodin Bidirectionally Modulates Macrophage Polarization and Epigenetically Regulates Macrophage Memory

Iwanowycz

Wang

Altomare

et al. 2016

Journal of Biological Chemistry

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Macrophages are pleiotropic cells capable of performing a broad spectrum of functions. Macrophage phenotypes are classified along a continuum between the extremes of proinflammatory M1 macrophages and anti-inflammatory M2 macrophages. The seemingly opposing functions of M1 and M2 macrophages must be tightly regulated for an effective and proper response to foreign molecules or damaged tissue. Excessive activation of either M1 or M2 macrophages contributes to the pathology of many diseases. Emodin is a Chinese herb-derived compound and has shown potential to inhibit inflammation in various settings. In this study, we tested the ability of emodin to modulate the macrophage response to both M1 and M2 stimuli. Primary mouse macrophages were stimulated with LPS/IFN␥ or IL4 with or without emodin, and the effects of emodin on gene transcription, cell signaling pathways, and histone modifications were examined by a variety of approaches, including microarray, quantitative real-time PCR, Western blotting, chromatin immunoprecipitation, and functional assays. We found that emodin bidirectionally tunes the induction of LPS/IFN␥-and IL4-responsive genes through inhibiting NFB/IRF5/STAT1 signaling and IRF4/STAT6 signaling, respectively. Thereby, emodin modulates macrophage phagocytosis, migration, and NO production. Furthermore, emodin inhibited the removal of H3K27 trimethylation (H3K27m3) marks and the addition of H3K27 acetylation (H3K27ac) marks on genes required for M1 or M2 polarization of macrophages. In conclusion, our data suggest that emodin is uniquely able to suppress the excessive response of macrophages to both M1 and M2 stimuli and therefore has the potential to restore macrophage homeostasis in various pathologies.

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Emodin has a cytotoxic activity against human multiple myeloma as a Janus-activated kinase 2 inhibitor

Cited by 118 publications

References 52 publications

Screening for novel quorum-sensing inhibitors to interfere with the formation of Pseudomonas aeruginosa biofilm

Screening for novel quorum-sensing inhibitors to interfere with the formation of Pseudomonas aeruginosa biofilm

Synergistic effect of emodin in combination with ampicillin or oxacillin against methicillin-resistantStaphylococcus aureus

Emodin Bidirectionally Modulates Macrophage Polarization and Epigenetically Regulates Macrophage Memory

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