Macrophage targeting contributes to the inhibitory effects of embelin on colitis-associated cancer

Wu, Ting; Dai, Yun; Wang, Weihong; Teng, Guigen; Jiao, Hongmei; Shuai, Xiaowei; Zhang, Rongxin; Zhao, Peng; Qiao, Liang

doi:10.18632/oncotarget.6969

Cited by 25 publications

(20 citation statements)

References 40 publications

(58 reference statements)

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“…In this context, it has been described that extended infiltration of neutrophils and production of ROS in cisplatin‐induced nephrotoxicity . In one reported literature, Wu et al has demonstrated inhibitory effects of embelin on colitis‐associated cancer through reducing an increased level of NF‐κB, TNF‐α, and IL1β . In another study, Meng et al have shown an anti‐inflammatory and antioxidant effect of embelin in myocardial infarction .…”

Section: Discussionsupporting

confidence: 85%

Embelin attenuates cisplatin‐induced nephrotoxicity: Involving inhibition of oxidative stress and inflammation in addition with activation of Nrf‐2/Ho‐1 pathway

Qin¹,

Meghana²,

Sowjanya³

et al. 2019

BioFactors

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In kidneys, elevated levels of inflammatory cytokines and oxidative stress were observed in nephrotoxicity triggered by cisplatin. Embelin has the anti-inflammatory property. It also got anti-tumorigenic and antioxidant properties. In this research, we analyzed the actions of embelin on nephrotoxicity triggered by cisplatin and vital actions by which it increases antioxidant actions and corrects the inflammation after embelin administration during nephrotoxicity triggered by cisplatin. Kidney function markers including blood urea nitrogen; serum creatinine; the markers of oxidative stress like malondialdehyde (MDA), antioxidant systems like glutathione, superoxide dismutase, glutathione S-transferase, catalase, and glutathione reductase; inflammation markers like nuclear factor-κB (NF-κB), tumor necrosis factor-α (TNF-α), and interleukin-1 beta (IL-1β); and the extent of nuclear factor-erythroid-2 p45-related factor-2 (Nrf2) and heme oxygenase-1 (HO-1) were determined. Histopathology studies of kidneys were also used to analyze nephrotoxicity induced by cisplatin. Treatment with embelin (25 and 50 mg/kg) upgrades the function of kidneys, by elevating antioxidant levels and reducing the MDA level in cisplatin-administered rats. Embelin treatment demonstrated a significant curtailment of oxidative stress as well as increased the activities of antioxidant enzymes, endogenously. Cisplatin upregulates cytokines (i.e., TNF-α and IL-1β) and NF-κB, and downregulates Nrf2 and HO-1. Embelin treatment also reduced the infiltration of neutrophils in the renal tubules and thus reduced the level of histological impairment. The outcome of this study implements that the signaling pathway of Nrf2/HO-1 may be the principal mechanism of embelin for protection from nephrotoxicity triggered by cisplatin, and thus, embelin diminishes oxidative stress and inflammation by impeding NF-κB.

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Section: Discussionsupporting

confidence: 85%

Embelin attenuates cisplatin‐induced nephrotoxicity: Involving inhibition of oxidative stress and inflammation in addition with activation of Nrf‐2/Ho‐1 pathway

Qin¹,

Meghana²,

Sowjanya³

et al. 2019

BioFactors

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“…It decreases the expression and production of pro-inflammatory cytokines and impairs the infiltration and function of tumor-associated macrophage (TAM) in the tumor milieu. 33 Our finding suggests that myeloid cells may be a critical target of embelin to achieve its therapeutic benefits in CAC.…”

Section: Introductionmentioning

confidence: 72%

“…We have previously reported that embelin not only resolved the colonic inflammation but also dramatically inhibited the colitis-associated tumor initiation and progression in an azoxymethane (AOM)/dextran sulfate sodium (DSS)induced CAC model. 32,33 Moreover, embelin treated mice exhibited a lower mortality rate than untreated controls during CAC challenge ( Figure 1A), suggesting that embelin significantly improves the long-term survival rate of tumorbearing mice. In addition, the spleen size of embelin-treated CAC-bearing mice was smaller than that of untreated group ( Figure 1B).…”

Section: Embelin Decreases Mdsc Accumulation In Spleen and Tumor In Cmentioning

confidence: 94%

“…29,30 Our previous studies have shown that embelin has potent antiinflammatory and anti-tumor effects in a CAC model. [31][32][33] Embelin can not only inhibit cancer cell proliferation but also modulate the TME. It decreases the expression and production of pro-inflammatory cytokines and impairs the infiltration and function of tumor-associated macrophage (TAM) in the tumor milieu.…”

Section: Introductionmentioning

confidence: 99%

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Embelin impairs the accumulation and activation of MDSCs in colitis-associated tumorigenesis

Wang

et al. 2018

OncoImmunology

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Myeloid-derived suppressor cells (MDSCs) are a major component of the immunosuppressive tumor microenvironment and has been recognized as a contributing factor for inflammation-related cancers. We previously showed that embelin has potent anti-inflammatory and anti-tumor effects in a colitisassociated cancer (CAC) model. Here, by using this model, we assessed the effect of embelin on the accumulation and suppressive function of MDSCs. We have demonstrated that embelin substantially reduced accumulation of MDSCs in the peripheral lymphoid organ and tumor tissue of CAC-bearing mice. Embelin impaired immunosuppressive activity of MDSCs by reducing the generation of reactive oxygen species (ROS) and arginase 1 level, leading to restored T cell responses. In tumor milieu, embelin increased the infiltration of CD8 + T cells, NK cells and mature dendritic cells whilst depleted the regulatory T cells. Moreover, embelin could directly interfere with the generation and function of MDSCs in vitro. These effects of embelin on MDSCs were mediated largely via limiting C/EBPβ and STAT3 signaling. Our findings support the hypothesis that embelin may be a promising pharmacologic agent in regulating MDSC-mediated immune tolerance in colorectal cancer.

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“…*Also obtained from stokes of Caragana jubata ** Black currants, apples and cherries are also good sources of quercetin Aloe-emodin, a natural compound extract from Aloe Vera, has been discovered to suppress cell proliferation and accelerate apoptosis in a variety of tumor cells [514].…”

Section: Mundulea Sericeamentioning

confidence: 99%

Alternative Treatments for Cancer Prevention and Cure [Part 1]

Mohiuddin¹

2019

APCT

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Many lay people along with some so called "key opinion leaders" have a common slogan "There's no answer for cancer". Again, mistake delays proper treatment and make situation worse, more often. Compliance is crucial to obtain optimal health outcomes, such as cure or improvement in QoL. Patients may delay treatment or fail to seek care because of high out-of-pocket expenditures. Despite phenomenal development, conventional therapy falls short in cancer management. There are two major hurdles in anticancer drug development: dose-limiting toxic side effects that reduce either drug effectiveness or the QoL of patients and complicated drug development processes that are costly and time consuming. Cancer patients are increasingly seeking out alternative medicine and might be reluctant to disclose its use to their oncology treatment physicians. But there is limited available information on patterns of utilization and efficacy of alternative medicine for patients with cancer. As adjuvant therapy, many traditional medicines shown efficacy against brain, head and neck, skin, breast, liver, pancreas, kidney, bladder, prostate, colon and blood cancers. The literature reviews non-pharmacological interventions used against cancer, published trials, systematic reviews and meta-analyses.

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Macrophage targeting contributes to the inhibitory effects of embelin on colitis-associated cancer

Cited by 25 publications

References 40 publications

Embelin attenuates cisplatin‐induced nephrotoxicity: Involving inhibition of oxidative stress and inflammation in addition with activation of Nrf‐2/Ho‐1 pathway

Embelin attenuates cisplatin‐induced nephrotoxicity: Involving inhibition of oxidative stress and inflammation in addition with activation of Nrf‐2/Ho‐1 pathway

Embelin impairs the accumulation and activation of MDSCs in colitis-associated tumorigenesis

Alternative Treatments for Cancer Prevention and Cure [Part 1]

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