The potential use of tideglusib as an adjuvant radio-therapeutic treatment for glioblastoma multiforme cancer stem-like cells

Bou-Gharios, Jolie; Assi, Sahar; Bahmad, Hisham F.; Kharroubi, Hussein; Araji, Tarek; Chalhoub, Reda M; Ballout, Farah; Harati, Hayat; Fares, Youssef; Abou-Kheir, Wassim

doi:10.1007/s43440-020-00180-5

Cited by 13 publications

(6 citation statements)

References 47 publications

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“…Collectively, we have investigated the GSK-3β binding capacity of 15 natural products, three of which have been previously shown to interfere with GSK-3β activity (obacunone (5), gedunin (4) and cedrelone (10)). These 15 compounds display a range of affinity for GSK-3β characterized by empirical energies of interaction ΔE ranging from -37.9 to -74.9 kcal/mol, for calodendrolide (17) and nomilin (7), respectively (Figure 7). We were able to identify two new natural products with ΔE comparable to those measured with the two reference inhibitors LY2090314 (3) and AR-A014418 (2): kihadanin B (9) and nomilin (7).…”

Section: Discussionmentioning

confidence: 99%

“…Beyond PSP, tideglusib ( 1 ) is a drug candidate considered today for the treatment of amyotrophic lateral sclerosis, [ 15 ] myotonic dystrophy type 1, [ 16 ] and some cancers. [ 17 ] Another potent GSK‐3β inhibitor is LY2090314 ( 3 ) (IC 50 = 250 nM) proposed for the treatment of pancreatic cancer in combination with nab‐paclitaxel. [ 18 ] This compound has revealed marked anticancer activities in animal models and in human.…”

Section: Introductionmentioning

confidence: 99%

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confidence: 99%

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Molecular docking study of GSK‐3β interaction with nomilin, kihadanin B, and related limonoids and triterpenes with a furyl‐δ‐lactone core

Vergoten

Bailly

2022

J Biochem & Molecular Tox

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Glycogen synthase kinase‐3β (GSK‐3β) is a target enzyme considered for the treatment of multiple human diseases, from neurodegenerative pathologies to viral infections and cancers. Numerous inhibitors of GSK‐3β have been discovered but thus far only a few have reached clinical trials and only one drug, tideglusib (1), has been registered. Natural products targeting GSK‐3β have been identified, including the two anticancer limonoids obacunone (5) and gedunin (4), both presenting a furyl‐δ‐lactone core. To help identifying novel GSK‐3β ligands, we have performed a molecular docking study with 15 complementary natural products bearing a furyl‐δ‐lactone unit (such as limonin (6) and kihadanins A (8) and B (9)) or a closely related structure (such as cedrelone (10) and nimbolide (11)). The formation of GSK‐3β‐binding complexes for those natural products was compared to reference GSK‐3β ATP‐competitive inhibitors LY2090314 (3) and AR‐A014418 (2). Our in silico analysis led to the identification of two new GSK‐3β‐binding natural products: kihadanin B (9) and nomilin (7). The latter surpassed the reference compounds in terms of calculated empirical energy of interaction (ΔE). Nomilin (7) can possibly bind to the active site of GSK‐3β, notably via the furyl‐δ‐lactone core and its 1‐acetyl group, implicated in the protein interaction. Compound structure‐binding relationships are discussed. The study should help the discovery of novel natural products targeting GSK‐3β.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Molecular docking study of GSK‐3β interaction with nomilin, kihadanin B, and related limonoids and triterpenes with a furyl‐δ‐lactone core

Vergoten

Bailly

2022

J Biochem & Molecular Tox

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“…However, few in vitro results deserve our attention [ 265 , 266 ]. By combining TDG with X-ray radiation treatment on 2D and 3D cultured GBM-derived U251 and U118 cells, Fares and Abou-Kheir’s teams found reduced cell proliferation, cell viability, and migration in a dose- and time-dependent manner [ 267 ]. These results suggest strongly that TDG may serve as a potential adjuvant radiotherapeutic agent to better target GBM tumors.…”

Section: Innovative Therapeutic Strategies Targeting Tau Protein For ...mentioning

confidence: 99%

Tau Protein as Therapeutic Target for Cancer? Focus on Glioblastoma

Hedna

Kovacic

Pagano

et al. 2022

Cancers

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Despite being extensively studied for several decades, the microtubule-associated protein Tau has not finished revealing its secrets. For long, Tau has been known for its ability to promote microtubule assembly. A less known feature of Tau is its capability to bind to cancer-related protein kinases, suggesting a possible role of Tau in modulating microtubule-independent cellular pathways that are associated with oncogenesis. With the intention of finding new therapeutic targets for cancer, it appears essential to examine the interaction of Tau with these kinases and their consequences. This review aims at collecting the literature data supporting the relationship between Tau and cancer with a particular focus on glioblastoma tumors in which the pathological significance of Tau remains largely unexplored. We will first treat this subject from a mechanistic point of view showing the pivotal role of Tau in oncogenic processes. Then, we will discuss the involvement of Tau in dysregulating critical pathways in glioblastoma. Finally, we will outline promising strategies to target Tau protein for the therapy of glioblastoma.

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“…Glycogen synthesis kinase 3-β (GSK3-β) has been implicated in many tumors including GBM, which paves the way for potential therapeutic strategies. [198][199][200] GSK3-β is a serine/threonine kinase 201 linked to several pathways involved in tumorigenesis, such as Wnt/β-catenin 202 and PI3K/PTEN. 203 One study showed that, in vivo, infrared (IR)-induced inhibition of GSK3-β reduced the tumor load, thus extending survival.…”

Section: Gsk3-β Inhibitorsmentioning

confidence: 99%

Repurposing of Anticancer Stem Cell Drugs in Brain Tumors

Bahmad

Daher

Aljamal

et al. 2021

J Histochem Cytochem.

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Brain tumors in adults may be infrequent when compared with other cancer etiologies, but they remain one of the deadliest with bleak survival rates. Current treatment modalities encompass surgical resection, chemotherapy, and radiotherapy. However, increasing resistance rates are being witnessed, and this has been attributed, in part, to cancer stem cells (CSCs). CSCs are a subpopulation of cancer cells that reside within the tumor bulk and have the capacity for self-renewal and can differentiate and proliferate into multiple cell lineages. Studying those CSCs enables an increasing understanding of carcinogenesis, and targeting CSCs may overcome existing treatment resistance. One approach to weaponize new drugs is to target these CSCs through drug repurposing which entails using drugs, which are Food and Drug Administration–approved and safe for one defined disease, for a new indication. This approach serves to save both time and money that would otherwise be spent in designing a totally new therapy. In this review, we will illustrate drug repurposing strategies that have been used in brain tumors and then further elaborate on how these approaches, specifically those that target the resident CSCs, can help take the field of drug repurposing to a new level.

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The potential use of tideglusib as an adjuvant radio-therapeutic treatment for glioblastoma multiforme cancer stem-like cells

Cited by 13 publications

References 47 publications

Molecular docking study of GSK‐3β interaction with nomilin, kihadanin B, and related limonoids and triterpenes with a furyl‐δ‐lactone core

Molecular docking study of GSK‐3β interaction with nomilin, kihadanin B, and related limonoids and triterpenes with a furyl‐δ‐lactone core

Tau Protein as Therapeutic Target for Cancer? Focus on Glioblastoma

Repurposing of Anticancer Stem Cell Drugs in Brain Tumors

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