8-bromo-7-methoxychrysin Reversed M2 Polarization of Tumor-associated Macrophages Induced by Liver Cancer Stem-like Cells

Sun, Shi; Cui, Yinghong; Ren, Kai; Quan, Meifang; Song, Zhenwei; Zou, Hui; Li, Duo; Zheng, Yu; Cao, Ji

doi:10.2174/1871520616666160204112556

Cited by 23 publications

(15 citation statements)

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“…Chrysin, a natural flavones, has been reported antitumor activities in various cancers [ 15 , 16 ]. Importantly, chrysin and its novel synthetic analogue 8-bromo-7-methoxychrysin (BrMC) targeted for inhibiting stemness in HCC cells [ 17 – 19 ]. Interestingly, 8-bromo-7-methoxychrysin (BrMC) suppressed stemness of SMMC-7721 cells induced by HSC-CM from LX-2 cells activated by SMMC-7721-derived LCSLCs [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE: 8-bromo-7-methoxychrysin suppress stemness of SMMC-7721 cells induced by co-culture of liver cancer stem-like cells with hepatic stellate cells

Zhou

Liu

et al. 2019

BMC Cancer

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BackgroundOur previous works have demonstrated that 8-bromo-7-methoxychrysin suppressed stemness of human hepatocellular carcinoma (HCC) cell line SMMC-7721 induced by condition medium from hepatic stellate cell line LX-2 that was activated by liver cancer stem-like cells (LCSCs). However, whether and whereby BrMC inhibits the stemness induced by co-culture of LCSCs and LX-2 cells remains to be investigated.MethodsThe second-generation spheres by sphere culture were identified and used as SMMC-7721-and MHCC97H-derived LCSLCs. SMMC-7721-and MHCC97-derived LCSCs/LX-2 cells transwell co-culture system was treated with BrMC and its lead compound chrysin. The concentrations of IL-6, IL-8, HGF and PDGF in condition medium from co-culture were measured by enzyme-linked immunosorbent assay (ELISA). The stemness of SMMC-7721 cells was evaluated by sphere formation assay and western blot analysis for expression levels of cancer stem cell markers (CD133 and CD44).The expression levels of cancer-associated fibroblast markers (FAP-α and α-SMA) were employed to evaluate pathologic activation of LX-2 cells. Addition of IL-6 and/or HGF or deletion of IL-6 and/or HGF was conducted to investigate the mechanisms for BrMC and chrysin treatment in SMMC-7721-derived LCSLCs co-cultured with LX-2cells.ResultsThe co-culture of LCSLCs with LX-2 cells increased sphere formation capability as well as expression of CD133 and CD44 in SMMC-7721 cells, meanwhile, upregulated expression of FAP-α in LX-2 cells. ELISA indicated that the concentrations of IL-6 and HGF were significantly elevated in Co-CM than that of condition media from co-cultured SMMC-7721 cells/LX-2 cells. Treatment of BrMC and chrysin with co-cultures of SMMC-7721- and MHCC97H-derived LCSLCs and LX-2 cells effectively inhibited the above responses. Moreover, addition of IL-6 and/or HGF induced stemness of SMMC-7721 cells and activation of LX-2 cells, conversely, deletion of IL-6 and/or HGF suppressed those. Furthermore, the inhibitory effects of BrMC and chrysin on stemness of SMMC-7721 cells and activation of LX-2 cells were attenuated by addition of IL-6 or HGF, and enhanced by deletion of IL-6 or HGF.ConclusionsOur results suggest IL-6 and HGF may be the key communication molecules for the interaction between LCSLCs and HSCs, and BrMC and chrysin could block these effects and be the novel therapeutic candidates for HCC management.

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Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE: 8-bromo-7-methoxychrysin suppress stemness of SMMC-7721 cells induced by co-culture of liver cancer stem-like cells with hepatic stellate cells

Zhou

Liu

et al. 2019

BMC Cancer

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“…Recently, we have reported that BrMC effectively inhibited CSC characteristics in hepatocellular carcinoma 26. More recently, we showed that reversed M2 polarization of TAMs by inhibition of NF-κB activation 25. In this study, we found that BrMC and SN50 alone or in combination could inhibit the expression of NF-κBp65 and FoxM1, sphere and colony formation and the expression of CD133, CD44, Bmi1 and Oct4 in H460 cells induced by pro-inflammatory cytokines, whereas, overexpression of NF-ĸBp65 almost abrogated the above effects of BrMC.…”

Section: Discussionmentioning

confidence: 93%

“…Our recent study demonstrated that 8-bromine-7-methoxychrysin (BrMC), a novel analogue of chrysin inhibits the malignant potential of cancer stem cells of hepatocellular carcinoma in vitro and in vivo 12. BrMC also can effectually reverse the M2 polarization of tumor associated macrophages by inhibiting NF-κB activation 25. For this reason, the purpose of this study was to evaluate whether BrMC can inhibit lung cancer stemness in H460 cells administered TNF-α after prolonged induction by TGF-β.…”

Section: Introductionmentioning

confidence: 99%

8-bromo-7-methoxychrysin targets NF-κB and FoxM1 to inhibit lung cancer stem cells induced by pro-inflammatory factors

Yuan¹,

Wen²,

Xu³

et al. 2019

J. Cancer

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We have previously reported that 8-bromo-7-methoxychrysin (BrMC), a novel synthetic derivative of chrysin, was demonstrated anti-tumor activities against several human cancers, including lung cancer. Interaction between inflammation and cancer stem cell are recently increasingly recognized in tumorigenesis and progression. The purpose of this study was to investigate whether BrMC inhibits lung cancer stemness of H460 cells induced by inflammatory factors (TGF-β combined with TNF-α) and its potential mechanism. Our results showed that BrMC inhibited lung cancer stemness, as validated by enhanced self-renewal ability, higher in vitro tumorigenicity, and increased expression of CD133, CD44, Bmi1 and Oct4 in H460 cells administered TNF-α after prolonged induction by TGF-β, in a concentration-dependent manner. Both NF-κB inhibition by SN50 and FoxM1 suppression by thiostrepton (THI) prompted the inhibition of BrMC on lung CSCs. Conversely, overexpression of NF-κBp65 significantly antagonized the above effects of BrMC. Meanwhile, overexpression of FoxM1 also significantly compromised BrMC function on suppression of FoxM1 and NF-κBp65 as well as stemness of lung CSCs. Our results suggest that activation of NF-κB and FoxM1 by cytokines facilitate the acquisition CSCs phenotype, and compromise the chemical inhibition, which may represent an effective therapeutic target for treatment of human lung cancer. Moreover, BrMC may be a potential promising candidate for targeting NF-κB/ FoxM1 to prevent the tumorigenesis under inflammatory microenvironment.

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“…Still, the authors of the study suggested that the cytotoxic effect of baicalein on breast cancer cells directly is more pronounced than on TAMs ( It has been reported that a novel chrysin (5,7-dihydroxyflavone) analog 8-bromo-7-methoxychrysin has anticancer activities with more potent bioactivity than the lead compound [60]. It also has the capacity to regulate the tumor microenvironment by inhibition of NF-κB activation, suppressing significantly the expression of the M2 macrophage marker CD163 and modulating the secretion profile of TAM cytokines [61].…”

Section: Flavonoidsmentioning

confidence: 99%

Targeting Tumor-Associated Macrophages by Plant Compounds

Grigore¹

2021

Macrophages

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Macrophages play an important role in cancer development, as they represent almost half of the cells forming the tumor microenvironment. They are called tumor-associated macrophages (TAMs) and most of them are alternative activated macrophages (M2 polarized), promoting cancer progression, angiogenesis and local immunosuppression. Blocking the macrophages recruitment, preventing their activation or turning M2 cells toward M1 phenotype (classic activated macrophage promoting an efficient immune response) is a modern immunotherapeutic approach for fighting cancer. Several studies showed that plant compounds (phenolics, triterpenes, coumarins, etc.) exert antitumor properties, not only by a direct toxical effect to malignant cells but also by influencing macrophage phenotypic differentiation.

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8-bromo-7-methoxychrysin Reversed M2 Polarization of Tumor-associated Macrophages Induced by Liver Cancer Stem-like Cells

Abstract: BrMC may be a potentially novel flavonoid agent that can be applied for disrupting the interaction of LCSLCs and TAMs.

Cited by 23 publications

References 0 publications

RETRACTED ARTICLE: 8-bromo-7-methoxychrysin suppress stemness of SMMC-7721 cells induced by co-culture of liver cancer stem-like cells with hepatic stellate cells

RETRACTED ARTICLE: 8-bromo-7-methoxychrysin suppress stemness of SMMC-7721 cells induced by co-culture of liver cancer stem-like cells with hepatic stellate cells

8-bromo-7-methoxychrysin targets NF-κB and FoxM1 to inhibit lung cancer stem cells induced by pro-inflammatory factors

Targeting Tumor-Associated Macrophages by Plant Compounds

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