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Nutraceuticals as Supplements for Cancer Prevention
Published in Sheeba Varghese Gupta, Yashwant V. Pathak, Advances in Nutraceutical Applications in Cancer, 2019
Nicholas Micciche, Brianna Choyce, Yashwant V. Pathak
Notch signaling, a protective biological mechanism, is a characteristic pathway of multicellular organisms. This pathway, which helps to regulate the fate of cells during the cell cycle, becomes active when signaled to renew stem cells. Genetic predispositions for notch receptor overactivation have been implicated in the formation of several types of cancers [32]. Ginger and many of its derivatives have been found to interfere with the notch signaling pathway by reducing its activity and the expression of target proteins [33]. This type of stop-it-before-it-starts mechanism makes notch signaling an important target in cancer prevention.
The Mechanisms Behind Tumour Repopulation
Published in Loredana G. Marcu, Iuliana Toma-Dasu, Alexandru Dasu, Claes Mercke, Radiotherapy and Clinical Radiobiology of Head and Neck Cancer, 2018
Loredana G. Marcu, Iuliana Toma-Dasu, Alexandru Dasu, Claes Mercke
Notch signalling is mainly involved in cellular communication, including CSCs, immune cells and vascular endothelial cells, and has several functional roles. Crosstalk with other pathways can also dictate the overall effect of Notch signalling. While Notch was found to be oncogenic in several tumour types, HNC mutations identified in Notch receptors suggested a tumour-suppressive function (Agrawal et al. 2011). The role of Notch1 as a tumour suppressor in HNC was suggested due to the loss-of-function mutations detected in a subgroup of patients. A more recent study revealed a dual role of Notch1 in HNC (Rettig et al. 2015), which varies from tumour to tumour among HNC, based on the pattern of NICD1 (Notch1 intracellular domain) expression, which is also associated with clinical outcome. Thus, while in a subgroup of HNC patients the Notch pathway activation has tumour suppression ability, in another subgroup has oncogenic properties. From a clinical perspective, Notch-targeted therapies could be personalised based on biomarkers of Notch1 activity (Rettig et al. 2015).
Overview of Angiogenesis: Molecular and Structural Features
Published in Robert J. Gropler, David K. Glover, Albert J. Sinusas, Heinrich Taegtmeyer, Cardiovascular Molecular Imaging, 2007
Arye Elfenbein, Michael Simons
More specifically, Notch signaling is responsible for the type of intercellular signaling that is known as lateral inhibition. This mode of developmental signaling enables different fates of differentiation to be selected within a homogenous group of cells (33). The Notch receptors (Notch 1–4) are cell membrane proteins that are cleaved upon binding of their (also membrane-bound) ligands, including Delta-1, -3, -4 and Jagged-1, -2, typically from another cell. Upon protein cleavage, the intracellular domain subsequently translocates to the nucleus and affects the transcription of target genes.
Bone morphogenetic protein (BMP)9 in cancer development: mechanistic, diagnostic, and therapeutic approaches?
Published in Journal of Drug Targeting, 2023
Ali G. Alkhathami, Mustafa Ryadh Abdullah, Muhjaha Ahmed, Hanan Hassan Ahmed, Sarab W. Alwash, Zahra Muhammed Mahdi, Fahad Alsaikhan, Ayed A. Dera
Aberrant activation Notch signalling and dysregulation of Notch receptors and ligands have been reported in several human tumours, including lung cancer, breast cancer, colorectal cancer, and prostate cancer. It has been shown that Notch receptors (Notch1 and Notch3) and ligands (JAG1, JAG2, and DLL3) were highly expressed and activated in osteosarcoma cells [38]. These ligands and receptors are involved in osteosarcoma cell proliferation and migration. Regarding BMP9 effects on this signalling pathway, it was indicated that BMP9 promotes 143B and MG63 cell cycle transition from S to G2 phase through upregulation and activation of Notch signalling in these cells. Since BMP9-induced cell progression was inhibited by blockade of Notch signalling, it was concluded that BMP9-dependent tumour growth relies on the Notch pathway [38].
Glycyrrhizin Mediates Downregulation of Notch Pathway Resulting in Initiation of Apoptosis and Disruption in the Cell Cycle Progression in Cervical Cancer Cells
Published in Nutrition and Cancer, 2022
Afza Ahmad, Rohit Kumar Tiwari, Mohd Saeed, Irfan Ahmad, Irfan Ahmad Ansari
The Notch signaling pathway plays a crucial mechanistic role in maintaining the balance involved in cell proliferation, survival, differentiation, and apoptosis (5). Earlier evidences substantiated that Notch signaling pathway is one of the most imperative signaling pathways in drug-resistant tumor cells. Furthermore, downregulation of Notch pathway could induce drug sensitivity, leading to increased inhibition of cancer cell growth, invasion, and metastasis (6). This signaling pathway comprises of four Notch receptors (Notch 1–4 in humans), a group of transmembrane proteins along with their ligands (Jagged1, two and delta-like ligand 1, 3, and 4). Binding of ligands with their Notch receptor on the adjacent cell would subsequently lead to the cleavage of Notch receptor by γ-secretase and concomitant release of the Notch intracellular domain (NICD). Constituently, active domain of Notch receptor, NICD translocate toward the nucleus and binds with numerous transcriptional regulators to induce the expression of target genes such as HES/HEY which in turn maintains stem cells via inhibiting the differentiation of cells (7–9). Different reports have demonstrated that increased expression of the Notch might be linked with the development of cervical carcinoma (10). Above-mentioned evidences promoted us to explore the plausible role of Notch signaling as a therapeutic intervention in CCa.
The role of the Notch pathway in the pathogenesis of systemic sclerosis: clinical implications
Published in Expert Review of Clinical Immunology, 2021
Filipe Seguro Paula, José Delgado Alves
The first in-human study using an anti-Notch mAb was with brontictuzumab [90], but again the gastrointestinal side effects were considerable, especially with the chronic use. Several others have been developed, mainly targeting the ligand-binding extracellular domains of the Notch receptors. It is noteworthy that one of them, by targeting specifically Notch1, averted the gastrointestinal toxicity in a preclinical study, supposedly by leaving the Notch2 signaling intact [89]. The same logic applies to a mAb against Notch-3, which would not produce goblet cell hyperplasia and diarrhea, as those effects are dependent on Notch-1/Notch-2 signaling. However, gastrointestinal side-effects still existed, including nausea and abdominal pain in up to 25% of participants of a phase I clinical trial [91], despite being reportedly well tolerated. Notch-3 inhibition could be helpful in patients with SSc as it is one of the two most important receptors in myofibroblasts and vascular smooth muscle cells.