Therapeutic Targets of the TNF Superfamily

Grewal, Iqbal S.

doi:10.1007/978-0-387-89520-8

Cited by 7 publications

(2 citation statements)

References 1,217 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…TNF receptors need an adaptor protein such as TNF receptor type 1-associated DEATH domain proteins (TRADDs), TNF receptor associated factors (TRAFs), receptor-interacting protein kinases (RIPs) and/or Fasassociated protein with death domain (FADD) [351]. TNFs, TNFRSFs as well as TRANCE, TRADDs, TRAFs and RIPSs and FADDs are of importance in the signaling and crosstalk with NF-jB [352,353].…”

Section: Nf-jb Signaling and Crosstalk During Carcinogenesis In Cell mentioning

confidence: 99%

NF-κB signaling and crosstalk during carcinogenesis

Brücher

Läng

Jamall

2019

4open

View full text Add to dashboard Cite

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.

show abstract

Section: Nf-jb Signaling and Crosstalk During Carcinogenesis In Cell mentioning

confidence: 99%

NF-κB signaling and crosstalk during carcinogenesis

Brücher

Läng

Jamall

2019

4open

View full text Add to dashboard Cite

show abstract

“…Reverse signaling through GITRL has been the subject of intense investigations. GITR −/− mice show decreased numbers of leukocytes in inflamed areas (89, 90), and treatment of experimental animals with GITR-Fc fusion protein ameliorates the symptoms of autoimmune or chronic inflammatory diseases (91). These effects may be due to induction of GITRL-mediated reverse signaling or blockage of GITR signaling (neutralizing GITRL).…”

Section: Glucocorticoid-induced Tnfr-related Protein (Gitr) Ligand (Gmentioning

confidence: 99%

Reverse Signaling of Tumor Necrosis Factor Superfamily Proteins in Macrophages and Microglia: Superfamily Portrait in the Neuroimmune Interface

et al. 2019

View full text Add to dashboard Cite

The tumor necrosis factor (TNF) superfamily (TNFSF) is a protein superfamily of type II transmembrane proteins commonly containing the TNF homology domain. The superfamily contains more than 20 protein members, which can be released from the cell membrane by proteolytic cleavage. Members of the TNFSF function as cytokines and regulate diverse biological processes, including immune responses, proliferation, differentiation, apoptosis, and embryogenesis, by binding to TNFSF receptors. Many TNFSF proteins are also known to be responsible for the regulation of innate immunity and inflammation. Both receptor-mediated forward signaling and ligand-mediated reverse signaling play important roles in these processes. In this review, we discuss the functional expression and roles of various reverse signaling molecules and pathways of TNFSF members in macrophages and microglia in the central nervous system (CNS). A thorough understanding of the roles of TNFSF ligands and receptors in the activation of macrophages and microglia may improve the treatment of inflammatory diseases in the brain and periphery. In particular, TNFSF reverse signaling in microglia can be exploited to gain further insights into the functions of the neuroimmune interface in physiological and pathological processes in the CNS.

show abstract

Chloroxylon swietenia (Roxb.) DC induces cell death and apoptosis by down‐regulating the NF‐κB pathway in MCF‐7 breast cancer cells: In vitro and in vivo investigations

et al. 2022

View full text Add to dashboard Cite

Background Natural products with targeted bioactivity have gained major attention in the field of cancer research owing to emerging anti‐cancer drug resistance and off target toxicities. Chloroxylon swietenia (Roxb.) DC is recognized as a folklore medicinal plant and has numerous therapeutic benefits in the folklore medicine system, however the anti‐cancer potential of this plant and its mechanism of action is poorly understood. Aims The aim of the study was to investigate the anti‐breast cancer efficacy of C. swietenia leaves methanol extract (CSLME) against MCF‐7 hormone dependent human breast cancer cell line with possible mechanism of action. Methods and results The anti‐breast cancer activity of CSLME against MCF‐7 cells was assessed by evaluating its efficacy toward cytotoxicity, cell migration, colony formation, DNA fragmentation, apoptosis, cytoskeleton, angiogenesis, cell cycle regulation, and animal toxicity. The preliminary screening of CSLME against MCF‐7 cells revealed the cytotoxicity (IC 50 20 μg/ml), inhibited cell migration, colony formation, and angiogenesis. It was observed that CSLME induces apoptosis by nuclear fragmentation and disruption of cytoskeleton by actin derangement. The results of Annexin V‐FITC assay and cell cycle analysis by flow cytometry clearly pointed out the sizable fraction of apoptotic cells, and arrested the cells at G2/M phase of cell cycle. The results of the immunoblotting experiments showed that CSLME activates intrinsic pathway of apoptosis with down regulation of anti‐apoptotic marker like Bcl2, up regulation of pro‐apoptotic markers like Bax & Bad, along with successful cleavage of Caspase‐9 and PARP‐1. Further, western blot analysis revealed the possible down regulation of NF‐κB pathway by CSLME, which may be responsible for anti‐cancer activity in MCF‐7 cells. In vivo animal model studies using NOD‐SCID mice demonstrated impressive anti‐tumor activity with significant reduction in tumor volume of MCF‐7 tumor xenograft. Of note, in‐vivo acute oral toxicity study as per Organization for Economic Cooperation and Development 423 revealed the nontoxic nature of CSLME. Conclusion The in vitro and in vivo findings clearly outline the potential of CSLME as inhibitor of growth and proliferation of MCF‐7 cells. Mechanistically, CSLME seems to activate intrinsic pathway of apoptosis, arrest cell cycle, target actin cytoskeleton, inhibit growth, colony formation, migration, and angiogenesis, with down regulation of NF‐κB pathway leading to cell death.

show abstract

Therapeutic Targets of the TNF Superfamily

Abstract: Expression of OX40 and OX40L Biologie Function of OX40-OX40L Interactions Expression and Role of OX40 and OX40Lin Disease 98 Intervention in OX40-OX40L Interaction for Therapy 100 Conclusion Contents xv 7. TARGETING CD70 FOR HUMAN THERAPEUTIC USE

Cited by 7 publications

References 1,217 publications

NF-κB signaling and crosstalk during carcinogenesis

NF-κB signaling and crosstalk during carcinogenesis

Reverse Signaling of Tumor Necrosis Factor Superfamily Proteins in Macrophages and Microglia: Superfamily Portrait in the Neuroimmune Interface

Chloroxylon swietenia (Roxb.) DC induces cell death and apoptosis by down‐regulating the NF‐κB pathway in MCF‐7 breast cancer cells: In vitro and in vivo investigations

Contact Info

Product

Resources

About