Cancer Chemopreventive Activities of Silibinin on Colorectal Cancer through Regulation of E-Cadherin/β-Catenin Pathway

Sameri, Saba; Saidijam, Massoud; Bahreini, Fatemeh; Najafi, Rezvan

doi:10.1080/01635581.2020.1800764

Cited by 32 publications

(18 citation statements)

References 45 publications

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“…It was revealed that 63% of the intervention group had ERERβ protein levels above the median and increased apoptotic markers, evaluated by TUNEL and caspase-3 [ 50 ]. A recent study demonstrated in vitro the inhibitory action of silibinin, an active constituent of the phytoestrogen Silymarin, on the β-catenin signaling pathway, a turning point of CRC tumorigenesis [ 51 ]. Angiogenesis, another hallmark of cancer, was strongly suppressed by silibinin, associated with the down-regulation of nitric oxide synthase (NOS), cyclooxygenases (COX), hypoxia-inducing factor-1 alpha (HIF-1 alpha) and vascular endothelial growth factor (VEGF) expression [ 52 ].…”

Section: Perspective In Humans and Chemopreventionmentioning

confidence: 99%

Estrogen Receptors in Colorectal Cancer: Facts, Novelties and Perspectives

et al. 2021

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Colorectal cancer (CRC) is the second cause of cancer-related death in both sexes worldwide. As pre-menopausal women are less likely to develop CRC compared to age-matched men, a protective role for estrogens has been hypothesized. Indeed, two isoforms of nuclear estrogen receptors (ER) have been described: ERα and ERβ. While the binding of 17beta-estradiol to ERα activates anti-apoptotic pathways, the interaction with ERβ activates caspase-3, inducing apoptosis. In this regard, several pieces of evidence show that ERβ tends to be under-regulated in advanced adenomas and CRC, with an opposite trend for ERα. Furthermore, ERβ stimulation slows adenomatous polyp growth and modulates relevant CRC pathways. Based on such considerations, dietary modulation of ER is promising, particularly in subjects with genetic predisposition for CRC. Nevertheless, the main limitation is the lack of clinical trials on a large population scale.

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Section: Perspective In Humans and Chemopreventionmentioning

confidence: 99%

Estrogen Receptors in Colorectal Cancer: Facts, Novelties and Perspectives

et al. 2021

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“…Metformin has been explored as a preventive agent for many cancers, including colorectal, lung, and breast, and has effects on EMT, in part through a reduction in WNT/β-catenin signaling [ 20 ]. Chemoprevention with silibinin has been used in colorectal and prostate models, where it attenuates EMT through changes in gene expression and effects on components of the tumor microenvironment [ 21 , 141 ]. In gastric cancer, β-carotene reduced EMT caused by tobacco exposure in mice [ 23 ].…”

Section: Frizzleds In Cancer Emtmentioning

confidence: 99%

“…Many of these markers are also mechanistically associated with EMT processes. Recent examples of approaches explored for cancer chemoprevention that target EMT include metformin, silibinin, β-carotene, and celecoxib [20][21][22][23]. The efficacy of chemopreventive drugs may depend on expression of targeted receptors, as with FZD9 and the lung cancer chemoprevention drug iloprost [8,24,25].…”

Section: Introductionmentioning

confidence: 99%

Cancer chemoprevention through Frizzled receptors and EMT

et al. 2021

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Frizzled (FZD) transmembrane receptors are well known for their role in β-catenin signaling and development and now understanding of their role in the context of cancer is growing. FZDs are often associated with the process of epithelial to mesenchymal transition (EMT) through β-catenin, but some also influence EMT through non-canonical pathways. With ten different FZDs, there is a wide range of activity from oncogenic to tumor suppressive depending on the tissue context. Alterations in FZD signaling can occur during development of premalignant lesions, supporting their potential as targets of chemoprevention agents. Agonizing or antagonizing FZD activity may affect EMT, which is a key process in lesion progression often targeted by chemoprevention agents. Recent studies identified a specific FZD as important for activity of an EMT inhibiting chemopreventive agent and other studies have highlighted the previously unrecognized potential for targeting small molecules to FZD receptors. This work demonstrates the value of investigating FZDs in chemoprevention and here we provide a review of FZDs in cancer EMT and their potential as chemoprevention targets.

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“…Silibinin, the most active flavinolignan has been revealed that it can suppress HCT-116 (Duke D stage of CRC) proliferation and migration and induced apoptosis. This drug can attenuate EMT through decreasing β-catenin gene, N-cadherin, and vimentin expression [30].…”

Section: Discussionmentioning

confidence: 99%

Differences in the Expression of β-Catenin Nucleus/Cytoplasm Ratio e-Cadherin and n-Cadherin and Correlation of β-Catenin Cytoplasm and Cadherin in Model of Duke D Stage Colorectal Cancer Cell Line

Winarko

Rahayu

Soeatmadji

et al. 2021

Open Access Maced J Med Sci

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BACKGROUND: β-catenin has a critical role in the homeostasis processes. Wnt/β-catenin signaling mainly involved in the modulation of cancer cell development. AIM: This research aimed to investigate the differences of β-catenin expression observed in the form of nucleus–cytoplasm ratio, the differences of E-cadherin and N-cadherin expressions, and the correlation between N-cadherin and E-cadherin and β-catenin cytoplasm in Dukes D stage colorectal cancer (CRC), which is an advanced stage and has experienced metastasis. MATERIALS AND METHODS: This study followed an experimental research design. The processes of culture manufacturing and subculture preparation of Dukes D stage CRC cell line model were performed before the administration of β-catenin, E-cadherin, and N-cadherin antibodies. The next process was staining using fluorescein-5-isothiocyanate and rhodamine, and observations were performed using a confocal microscope. The number of cells was counted, and the intensity of antibody expression based on the arbitrary unit was measured. RESULTS: There was a significant difference between the expression of β-catenin nucleus and cytoplasm expression (p = 0.00), as well as between E-cadherin expression and N-cadherin expression (p = 0.00). In addition, a correlation also existed between an increased N-cadherin expression and decreased E-cadherin expression and β-catenin cytoplasm in Dukes D stage CRC, but the results were not significant (p = 0.837 and p = 0.108). CONCLUSION: In advanced-stage CRC (Dukes D), the Wnt signaling proved to be active and was characterized by a high expression of β-catenin nucleus, it activates the target gene. Similarly, at the Dukes D stage, N-cadherin expression increased whereas E-cadherin expression decreased in which causing the translocation of β-catenin into the nucleus.

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Cancer Chemopreventive Activities of Silibinin on Colorectal Cancer through Regulation of E-Cadherin/β-Catenin Pathway

Cited by 32 publications

References 45 publications

Estrogen Receptors in Colorectal Cancer: Facts, Novelties and Perspectives

Estrogen Receptors in Colorectal Cancer: Facts, Novelties and Perspectives

Cancer chemoprevention through Frizzled receptors and EMT

Differences in the Expression of β-Catenin Nucleus/Cytoplasm Ratio e-Cadherin and n-Cadherin and Correlation of β-Catenin Cytoplasm and Cadherin in Model of Duke D Stage Colorectal Cancer Cell Line

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