Silibinin is a direct inhibitor of STAT3

Verdura, Sara; Cuyàs, Elisabet; Llorach-Parés, Laura; Pérez-Sánchez, Almudena; Micol, Vicente; Nonell-Canals, Alfons; Joven, Jorge; Valiente, Manuel; Sánchez-Martínez, Melchor; Bosch-Barrera, Joaquim; Menendez, Javier A.

doi:10.1016/j.fct.2018.04.028

Cited by 64 publications

(50 citation statements)

References 58 publications

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“…Matsuno et al and Xu et al described further double-digit micromolar STAT3 inhibitors, STX-0119 and Cpd30-12 (in cellular assays; Figure 3h,i) [72,73]. Furthermore, a number of natural products (or analogs thereof) and antioxidants have been proposed and identified as potential inhibitors of STATs, most particularly STAT3, displaying even single-digit micromolar inhibitory activities [74][75][76][77][78].…”

Section: Stat3 Inhibitorsmentioning

confidence: 98%

Direct Targeting Options for STAT3 and STAT5 in Cancer

Orlova

Wagner

Araujo

et al. 2019

Cancers

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Signal transducer and activator of transcription (STAT)3 and STAT5 are important transcription factors that are able to mediate or even drive cancer progression through hyperactivation or gain-of-function mutations. Mutated STAT3 is mainly associated with large granular lymphocytic T-cell leukemia, whereas mutated STAT5B is associated with T-cell prolymphocytic leukemia, T-cell acute lymphoblastic leukemia and γδ T-cell-derived lymphomas. Hyperactive STAT3 and STAT5 are also implicated in various hematopoietic and solid malignancies, such as chronic and acute myeloid leukemia, melanoma or prostate cancer. Classical understanding of STAT functions is linked to their phosphorylated parallel dimer conformation, in which they induce gene transcription. However, the functions of STAT proteins are not limited to their phosphorylated dimerization form. In this review, we discuss the functions and the roles of unphosphorylated STAT3/5 in the context of chromatin remodeling, as well as the impact of STAT5 oligomerization on differential gene expression in hematopoietic neoplasms. The central involvement of STAT3/5 in cancer has made these molecules attractive targets for small-molecule drug development, but currently there are no direct STAT3/5 inhibitors of clinical grade available. We summarize the development of inhibitors against the SH2 domains of STAT3/5 and discuss their applicability as cancer therapeutics.

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Section: Stat3 Inhibitorsmentioning

confidence: 98%

Direct Targeting Options for STAT3 and STAT5 in Cancer

Orlova

Wagner

Araujo

et al. 2019

Cancers

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“…It appears that the binding did not cause the conformational change of the proliferator-activated receptor. Verdura et al (2018) found that the silibinin was the sole signal transducer, and activator of transcription three inhibitor was predicted to form a hydrogen bond with DNA through interaction optimization performed by MD simulations. In addition, the enantioselective aquatic toxicity of chemicals could be also estimated.…”

Section: Development In Food Toxicology Via MD Simulationsmentioning

confidence: 99%

“…Hyperdynamics is another method involving AC MD simulation by lowering energy barriers, while performing the simulation of a nano/atomic system. MD simulations have also been widely used in the design of pharmaceuticals, materials used in bioinformatics, and molecular design of advanced materials (Řezanka, Stibor, Azizoglu, Turgut, & Pirinccioglu, 2016;Verdura et al, 2018;Zhuang, Zhang, & Liu, 2014). For example, Gupta, Nunes, Vyas, and Jonnalagadda (2011) evaluated solubility parameters and miscibility of pharmaceutical compounds using MD simulation, whereas Bermudez, Mortier, Rakers, Sydow, and Wolber (2016) used MD simulation to probe the conformational state of proteins.…”

Section: Introductionmentioning

confidence: 99%

Molecular Dynamics Simulation for Mechanism Elucidation of Food Processing and Safety: State of the Art

Chen

Huang

Miao

et al. 2018

Comp Rev Food Sci Food Safe

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Molecular dynamics (MD) simulation is a useful technique to study the interaction between molecules and how they are affected by various processes and processing conditions. This review summarizes the application of MD simulations in food processing and safety, with an emphasis on the effects that emerging nonthermal technologies (for example, high hydrostatic pressure, pulsed electric field) have on the molecular and structural characteristics of foods and biomaterials. The advances and potential projection of MD simulations in the science and engineering aspects of food materials are discussed and focused on research work conducted to study the effects of emerging technologies on food components. It is expected by showing key case studies that it will stir novel developments as a valuable tool to study the effects of emerging food technologies on biomaterials. This review is useful to food researchers and the food industry, as well as researchers and practitioners working on flavor and nutraceutical encapsulations, dietary carbohydrate product developments, modified starches, protein engineering, and other novel food applications.

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“…The polyphenolic flavonoid, Silibinin, is an extract from milk thistle (Silybum marianium) and was earlier reported to have an anticancer effect [394][395][396][397]. Silibinin is a direct STAT3 inhibitor [398] with no direct effect on apoptosis or changes in p53 and bcl2 [395]. Silibinin inhibits NF-jB p50 translocation via the upregulation of IjB and downregulates ZEB1 and Zinc finger protein SNAI2 (SLUG) transcription factors, and can reverse cell transition [399].…”

Section: Silibininmentioning

confidence: 99%

NF-κB signaling and crosstalk during carcinogenesis

Brücher

Läng

Jamall

2019

4open

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Transcription factors (TFs) are proteins that control the transcription of genetic information from DNA to mRNA by binding to specific DNA sequences either on their own or with other proteins as a complex. TFs thus support or suppress the recruitment of the corresponding RNA polymerase. In general, TFs are classified by structure or function. The TF, Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), is expressed in all cell types and tissues. NF-κB signaling and crosstalk are involved in several steps of carcinogenesis including in sequences involving pathogenic stimulus, chronic inflammation, fibrosis, establishment of its remodeling to the precancerous niche (PCN) and transition of a normal cell to a cancer cell. Triggered by various inflammatory cytokines, NF-κB is activated along with other TFs with subsequent stimulation of cell proliferation and inhibition of apoptosis. The involvement of NF-κB in carcinogenesis provides an opportunity to develop anti-NF-κB therapies. The complexity of these interactions requires that we elucidate those aspects of NF-κB interactions that play a role in carcinogenesis, the sequence of events leading to cancer.

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Silibinin is a direct inhibitor of STAT3

Cited by 64 publications

References 58 publications

Direct Targeting Options for STAT3 and STAT5 in Cancer

Direct Targeting Options for STAT3 and STAT5 in Cancer

Molecular Dynamics Simulation for Mechanism Elucidation of Food Processing and Safety: State of the Art

NF-κB signaling and crosstalk during carcinogenesis

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