Sulforaphane inhibits growth and blocks Wnt/β-catenin signaling of colorectal cancer cells

Bernkopf, Dominic B.; Daum, Gabriele; Brückner, Martina K.; Behrens, Jürgen

doi:10.18632/oncotarget.26125

Cited by 28 publications

(16 citation statements)

References 32 publications

(40 reference statements)

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“…Other chalcones including derricin and derricidin have also been reported to possess such effect when treated to HCT116 colon cancer cell line [ 20 ]. An isothiocyanate compound, sulforaphane, was reported to inhibit canonical Wnt transcriptional activity in two separate studies, as demonstrated by TCF/LEF reporter assays in breast CSCs and colorectal cancer cell lines SW480, DLD1 and HCT116 [ 21 , 22 ]. In this study, while isothiocyanate members consistently exhibited this effect, chalcones did not.…”

Section: Discussionmentioning

confidence: 99%

Identification of Phytochemical-Based β-Catenin Nuclear Localization Inhibitor in NSCLC: Differential Targeting Population from Member of Isothiocyanates

Heng

Cheah

2021

Molecules

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Decades of research has convinced us that phytochemical compounds contained within the plant products are the real deal, and they provide benefits such as health maintenance an d cure to illnesses. One of the deadliest noncommunicable diseases today is lung cancer, hence its disease management still deserves attention. Wnt/β-catenin pathway activation conferring cancer stem cell (CSC) activities to non-small cell lung carcinomas (NSCLCs) may explain why the disease is still difficult to cure. In the present study, we assessed several representatives of phytochemical categories consisting of alkaloids, chalcones and isothiocyanates for their inhibitory activity to nuclear localization of β-catenin—an important event for Wnt/β-catenin pathway activation, in lung cancer cell lines. Real-time cell analyzer confirmed that evodiamine (EVO), chelidonine (CHE), isoliquiritigenin (ISO), licochalcone-A (LICO), benzyl isothiocyanate (BI) and phenethylisothiocyanate (PI) exhibited anti-proliferative activities and cytotoxicities to adenocarcinoma cell line SK-LU-1 and human lung CSC primary cell line (HLCSC). Immunofluorescence assay identified that CHE, ISO, LICO, BI and PI were capable of reducing the number of cells harboring β-catenin within the nuclei of these cells. We extended the characterizations of BI and PI in Wnt-dependent squamous cell carcinoma cell line NCI-H1703 on several CSC functions and found that BI was better at inhibiting soft agar colony formation as an output of self-renewal ability, whereas PI was more effective in inhibiting the growth of multicellular tumor spheroid model mimicking micrometastases. Both however were not able to inhibit migration and invasion of NCI-H1703. In conclusion, BI could potentially be used as a safer alternative to target undifferentiated CSCs as adjuvant therapy, whereas PI could be used as chemotherapy to remove bulk tumor.

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Section: Discussionmentioning

confidence: 99%

Identification of Phytochemical-Based β-Catenin Nuclear Localization Inhibitor in NSCLC: Differential Targeting Population from Member of Isothiocyanates

Heng

Cheah

2021

Molecules

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“…Bernkopf et al . also pointed out that active WNT/β-catenin signaling pathway is the main driving force of colorectal cancer, while SFN can inhibit the growth of colorectal cancer, although no studies have shown a correlation between the two [ 12 ]. Toyama et al .…”

Section: Discussionmentioning

confidence: 99%

“…SFN decreases the activation of p63-iRHOM2 pathway in palmoplantar keratosis and squamous esophageal cancer syndrome (TOC) keratinocytes, leads to the decrease in oxidative stress, inflammation, proliferation and stress response K16, and increases apoptosis [ 11 ]. In addition, there is growing evidence that SFN can inhibit the growth of various types of cancer from different organs, which has aroused interest in the use of SFN in anti-cancer therapy [ 12 ]. The combination of SFN and quercetin has anti-migration effect on melanoma [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

Identification of sulforaphane regulatory network in hepatocytes by microarray data analysis based on GEO database

et al. 2021

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For the past several years, more and more attention has been paid to the exploration of traditional medicinal plants. Further studies have shown that more dietary consumption of cruciferous vegetables can prevent the occurrence of tumor, indicating the potential applications in the chemoprevention of cancer. Sulforaphane (SFN) has been identified by the National Cancer Institute as a candidate for chemopreventive research; it is one of several compounds selected by the National Cancer Institute’s Rapid Access to Preventive Intervention Development Program and is currently in use. In this study, based on the data of gene expression integrated database (GEO), the gene expression profile of hepatocytes that were treated with SFN was analyzed. The ANOVA and Limma packets in R were used to analyze the differentially expressed genes. On this basis, GO function and KEGG signaling pathway enrichment were further analyzed. The core gene HSP90AA1 was screened by PPI network established by STRING and Cytoscape software for further study. Finally, miRNAs targeted HSP90AA1 were predicted by miRanda. All in all, based on the data of GSE20479 chip, the molecular mechanism of SFN on hepatocytes was studied by a series of bioinformatics analysis methods, and it indicated that SFN might effect on the hepatocyte by regulating HSP90AA1.

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“…Various studies have demonstrated via many molecular mechanisms that SFN induces apoptosis and inhibits proliferation and migration in human colon cancer. [29][30][31][32] SFN can also activate the Nrf2 signaling pathway and protect against H2O2-mediated oxidative damage in normal colonic cells. 33 SAL exhibits antitumor, antibacterial, antifungal, antiparasitic, antiviral and anti-inflammatory activities.…”

Section: Discussionmentioning

confidence: 99%

<p>Salinomycin and Sulforaphane Exerted Synergistic Antiproliferative and Proapoptotic Effects on Colorectal Cancer Cells by Inhibiting the PI3K/Akt Signaling Pathway in vitro and in vivo</p>

Liu

Liu³

et al. 2020

OTT

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Background: Both salinomycin (SAL) and sulforaphane (SFN) exert their antitumorigenic effects in various types of cancer We investigated whether combining salinomycin (SAL, an antibiotic ionophore) with sulforaphane (SFN, a phytochemical) exerted synergistic antiproliferative and proapoptotic activities in colorectal cancer (CRC) cells in vitro and in vivo by evaluating the proliferative and apoptotic responses of two CRC cell lines. Materials and Methods: The combination index (CI) was calculated using the Chou-Talalay method, and the effects of the synergistic combination (CI<1) of lower doses of SAL and SFN were selected for further studies. Anti-tumor effect of the combination of SAL and SFN was tested both in vitro and in vivo. Results: Cotreatment effectively inhibited proliferation, migration and invasion and enhanced apoptosis. The xenograft model also showed similar results. Furthermore, we evaluated the molecular mechanism behind SAL-and SFN-mediated CRC cell apoptosis. The combination treatment induced apoptosis in Caco-2 and CX-1 cells by inhibiting the PI3K/Akt pathway, which increased the expression of the tumor suppressor protein p53. The treatment also decreased the expression of the survival protein Bcl-2 and increased the expression of the proapoptotic protein Bax, which increased the Bax/Bcl-2 ratio, as well as enhanced poly ADP-ribose polymerase (PARP) cleavage. Upon inhibiting the PI3K/Akt pathway with LY294002 prior to cotreatment, we detected enhanced PARP cleavage compared to that in the cotreatment only group. Conclusion: We investigated whether the combination of SAL and SFN had antiproliferative and proapoptotic effects in CRC cells both in vitro and in vivo. Cotreatment also significantly decreased migration and invasion compared to that of the control and SAL or SFN monotherapies. This novel combination of SAL and SFN might provide a potential strategy to treat CRC.

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Sulforaphane inhibits growth and blocks Wnt/β-catenin signaling of colorectal cancer cells

Cited by 28 publications

References 32 publications

Identification of Phytochemical-Based β-Catenin Nuclear Localization Inhibitor in NSCLC: Differential Targeting Population from Member of Isothiocyanates

Identification of Phytochemical-Based β-Catenin Nuclear Localization Inhibitor in NSCLC: Differential Targeting Population from Member of Isothiocyanates

Identification of sulforaphane regulatory network in hepatocytes by microarray data analysis based on GEO database

<p>Salinomycin and Sulforaphane Exerted Synergistic Antiproliferative and Proapoptotic Effects on Colorectal Cancer Cells by Inhibiting the PI3K/Akt Signaling Pathway in vitro and in vivo</p>

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