Sulforaphene enhances radiosensitivity of hepatocellular carcinoma through suppression of the NF‐κB pathway

Li, Zhen; Li, Yahua; Zhang, Wenzhe; Han, Xinwei

doi:10.1002/jbt.21917

Cited by 24 publications

(19 citation statements)

References 27 publications

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“…The response to curcumin was associated with the inhibition of NF-κB and downstream signaling such as MYC, JNK, Cyclin D1, and STAT3 [80]. Curcumin, as well as sulforaphane, a naturally occurring isothiocyanate found in cruciferous vegetables, has been shown to further sensitize human hepatocellular carcinoma cells to radiation through inhibition of radiation-induced NF-κB activity [104,105]. Besides natural compounds, NF-κB inhibitors have also been developed and tested in pre-clinical models.…”

Section: Nf-κb As a Target For Cancer Prevention And Therapymentioning

confidence: 99%

Context-Dependent Role of NF-κB Signaling in Primary Liver Cancer—from Tumor Development to Therapeutic Implications

Czauderna

Castven

Mahn

et al. 2019

Cancers

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Chronic inflammatory cell death is a major risk factor for the development of diverse cancers including liver cancer. Herein, disruption of the hepatic microenvironment as well as the immune cell composition are major determinants of malignant transformation and progression in hepatocellular carcinomas (HCC). Considerable research efforts have focused on the identification of predisposing factors that promote induction of an oncogenic field effect within the inflammatory liver microenvironment. Among the most prominent factors involved in this so-called inflammation-fibrosis-cancer axis is the NF-κB pathway. The dominant role of this pathway for malignant transformation and progression in HCC is well documented. Pathway activation is significantly linked to poor prognostic traits as well as stemness characteristics, which places modulation of NF-κB signaling in the focus of therapeutic interventions. However, it is well recognized that the mechanistic importance of the pathway for HCC is highly context and cell type dependent. While constitutive pathway activation in an inflammatory etiological background can significantly promote HCC development and progression, absence of NF-κB signaling in differentiated liver cells also significantly enhances liver cancer development. Thus, therapeutic targeting of NF-κB as well as associated family members may not only exert beneficial effects but also negatively impact viability of healthy hepatocytes and/or cholangiocytes, respectively. The review presented here aims to decipher the complexity and paradoxical functions of NF-κB signaling in primary liver and non-parenchymal cells, as well as the induced molecular alterations that drive HCC development and progression with a particular focus on (immune-) therapeutic interventions.

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Section: Nf-κb As a Target For Cancer Prevention And Therapymentioning

confidence: 99%

Context-Dependent Role of NF-κB Signaling in Primary Liver Cancer—from Tumor Development to Therapeutic Implications

Czauderna

Castven

Mahn

et al. 2019

Cancers

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“…Besides the MAPK signaling pathway, other pathways and mechanisms mediate the occurrence and development of multiple types of tumors induced by sulforaphene. An increasing number of studies have demonstrated that sulforaphene promotes tumorigenesis and metastasis through the regulation of cell proliferation, migration, invasion, and apoptosis [21]. Recently, sulforaphene was reported to inhibit tumor growth in colon cancer through the induction of glutathione ablation and microtubule depolymerization [26].…”

Section: Discussionmentioning

confidence: 99%

Sulforaphene induces apoptosis and inhibits the invasion of esophageal cancer cells through MSK2/CREB/Bcl-2 and cadherin pathway in vivo and in vitro

Zhang

et al. 2019

Cancer Cell Int

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Background: As a novel type of isothiocyanate derived from radish seeds from cruciferous vegetables, sulforaphene (SFE, 4-methylsufinyl-3-butenyl isothiocyanate) has various important biological effects, such as anti-oxidative and anti-bacterial effects. Recently, sulforaphene has attracted increasing attention for its anti-tumor effects and its ability to suppress the development of multiple tumors through different regulatory mechanisms. However, it has not yet been widely investigated for the treatment of esophageal cancer. Methods:We observed an increased apoptosis in esophageal cancer cells on sulforaphene treatment through flow cytometry (FCM) analysis and transmission electron microscopy (TEM). Through mass spectrometry (MS) analysis, we further detected global changes in the proteomes and phosphoproteomes of esophageal cancer cells on sulforaphene treatment. The molecular mechanism of sulforaphene was verified by western blot,the effect and mechanism of SFE on esophageal cancer was further verified by patient-derived xenograft mouse model. Results:We identified multiple cellular processes that were changed after sulforaphene treatment by proteomics. We found that sulforaphene could repress the phosphorylation of CREB through MSK2, leading to suppression of Bcl-2 and further promoted cell apoptosis. Additionally, we confirmed that sulforaphene induces tumor cell apoptosis in mice. Interestingly, we also observed the obvious inhibition of cell migration and invasion caused by sulforaphene treatment by inhibiting the expression of cadherin, indicating the complex effects of sulforaphene on the development of esophageal cancer. Conclusions:Our data demonstrated that sulforaphene induced cell apoptosis and inhibits the invasion of esophageal cancer through a mechanism involving the inhibition of the MSK2-CREB-Bcl2 and cadherin pathway. Sulforaphene could therefore serve as a promising anti-tumor drug for the treatment of esophageal cancer. BackgroundEsophageal cancer (EC) is one of the most aggressive and common malignancies of the digestive system worldwide and has the 7th highest morbidity rate and 6th highest mortality rate [1,2]. There are approximately 240,000 new cases of EC in China every year, and the 5-year overall survival rate for EC patients is still less than 25% [3,

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“…Ren et al found that radiation increased NF‐κB activity, while NF‐κB inhibitor enhanced radiation‐induced cell death. Blocking the NF‐κB pathway sensitized the radiosensitivity of HCC cells . NF‐κB in the irradiated cells determined radioresistance of the tumor cells .…”

Section: Discussionmentioning

confidence: 99%

Activation of PTGS2/NF‐κB signaling pathway enhances radiation resistance of glioma

Tan

Liu

et al. 2019

Cancer Medicine

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Objective We focused on the effects of PTGS2/NF‐κB signaling pathway on the radiation resistance of glioma in the study. Methods We downloaded the microarray data from the Gene Expression Omnibus (GEO) database. We verified transfection successfully through QRT‐PCR analysis. Immunofluorescence was used to detect γH2AX content under 2 Gy radiation. The survival rates of cells under 2 Gy irradiation were tested by clonogenic survival assay. Flow cytometry was used to detect cell cycle. Western blot was applied to detect the expression of NF‐κB pathway‐related proteins. We also used MTT assay to detect the proliferation of cells. Results In this research, we discovered that the expression of the PTGS2 was upregulated in radiation‐resistant glioma cells. The radio‐tolerance rate of U87 cells was obviously elevated after the overexpression of PTGS2. The radioresistance of U87R cells was significantly reduced after the knockdown of PTGS2. After radiotherapy, the number of cells arrested in G2/M phase decreased after PTGS2 overexpression in U87cells but increased in PTGS2 knockdown in U87R cells. The survival rate of U87 and U87R cells under radiation decreased significantly after the addition of NF‐κB inhibitor. The proliferation of U87 cells was suppressed by radiation and the addition of Bay 11. In addition, PTGS2 activated NF‐κB signaling pathway and prevented DNA damage after radiotherapy. Lastly, PTGS2 was proved to facilitate tumor cell proliferation and improve the radio‐tolerance. Conclusion PTGS2/NF‐κB signaling pathway was involved in radio‐tolerance of glioma cells, which provided a new insight into glioma therapy.

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Sulforaphene enhances radiosensitivity of hepatocellular carcinoma through suppression of the NF‐κB pathway

Cited by 24 publications

References 27 publications

Context-Dependent Role of NF-κB Signaling in Primary Liver Cancer—from Tumor Development to Therapeutic Implications

Context-Dependent Role of NF-κB Signaling in Primary Liver Cancer—from Tumor Development to Therapeutic Implications

Sulforaphene induces apoptosis and inhibits the invasion of esophageal cancer cells through MSK2/CREB/Bcl-2 and cadherin pathway in vivo and in vitro

Activation of PTGS2/NF‐κB signaling pathway enhances radiation resistance of glioma

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