Drugs That Inhibit Signalling Pathways for Tumor Cell Growth and Proliferation

Avendaño, Carmen; Menéndez, J. Carlos

doi:10.1016/b978-0-444-52824-7.00009-3

Cited by 15 publications

(7 citation statements)

References 117 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In this study, serine/threonine-protein kinase (SPK) was identified in H. longicornis saliva and this could constitute substantial functional implications given the key role of protein kinases (PTKs) in diverse biological activities. Serine/threonine-protein kinase is a type of PTK that orchestrates the regulation of proteins’ biological activities by phosphorylating the hydroxy group of serine and threonine, thus triggering a conformational change from an inactive to an active form of a protein ( Avendaño and Menéndez, 2008 ). Of note, many salivary peptides/proteins could affect the same host cell population (functional redundancy), and likewise, one salivary peptide/protein could target more than one host cell population (pluripotency) ( Aounallah et al., 2020 ), and these activities could be championed by the presence of serine/threonine-protein kinase.…”

Section: Discussionmentioning

confidence: 99%

Phosphoproteomic Analysis of Haemaphysalis longicornis Saliva Reveals the Influential Contributions of Phosphoproteins to Blood-Feeding Success

Agwunobi

Wang

Huang

et al. 2022

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

Tick saliva, an essential chemical secretion of the tick salivary gland, is indispensable for tick survival owing to the physiological influence it exerts on the host defence mechanisms via the instrumentality of its cocktail of pharmacologically active molecules (proteins and peptides). Much research about tick salivary proteome has been performed, but how most of the individual salivary proteins are utilized by ticks to facilitate blood acquisition and pathogen transmission is not yet fully understood. In addition, the phosphorylation of some proteins plays a decisive role in their function. However, due to the low phosphorylation level of protein, especially for a small amount of protein, it is more difficult to study phosphorylation. Maybe, for this reason, the scarcity of works on the phosphorylated tick salivary proteomes still abound. Here, we performed a phosphoproteomic analysis of Haemaphysalis longicornis tick saliva via TiO2 enrichment and the most advanced Thermo Fisher Orbitrap Exploris 480 mass spectrometer for identification. A total of 262 phosphorylated tick saliva proteins were identified and were subjected to functional annotation/enrichment analysis. Cellular and metabolic process terms accounted for the largest proportion of the saliva proteins, with the participation of these proteins in vital intracellular and extracellular transport-oriented processes such as vesicle-mediated transport, exocytic process, cell adhesion, and movement of cell/subcellular component. “Endocytosis”, “Protein processing in endoplasmic reticulum”, and “Purine metabolism” were the most significantly enriched pathways. The knockdown (RNAi) of Tudor domain-containing protein (TCP), actin-depolymerizing factors (ADF), programmed cell death protein (PD), and serine/threonine-protein kinase (SPK) resulted in the dissociation of collagen fibers and the pilosebaceous unit, increased inflammatory infiltrates/granulocytes (possibly heterophiles), and the depletion of the epithelium. Ticks injected with SPK dsRNA engorged normally but with a change in skin colour (possibly an autoimmune reaction) and the failure to produce eggs pointing to a possible role of SPK in reproduction and host immune modulation. Ticks injected with ADF dsRNA failed to acquire blood, underscoring the role of ADF in facilitating tick feeding. The results of this study showed the presence of phosphorylation in tick saliva and highlight the roles of salivary phosphoproteins in facilitating tick feeding.

show abstract

Section: Discussionmentioning

confidence: 99%

Phosphoproteomic Analysis of Haemaphysalis longicornis Saliva Reveals the Influential Contributions of Phosphoproteins to Blood-Feeding Success

Agwunobi

Wang

Huang

et al. 2022

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

show abstract

“…Protein phosphorylation is a recurring topic in medical science as the mechanism that regulates various cellular processes. Protein modification is catalysed by protein kinases that use ATP as the source of phosphate [1,2]. Protein kinases have become the aim of targeted therapy because they play a key role in proliferation, cell cycle, and cell death.…”

Section: Introductionmentioning

confidence: 99%

Inhibiting CK2 among Promising Therapeutic Strategies for Gliomas and Several Other Neoplasms

Pucko

Ostrowski

2022

Pharmaceutics

View full text Add to dashboard Cite

In gliomas, casein kinase 2 (CK2) plays a dominant role in cell survival and tumour invasiveness and is upregulated in many brain tumours. Among CK2 inhibitors, benzimidazole and isothiourea derivatives hold a dominant position. While targeting glioma tumour cells, they show limited toxicity towards normal cells. Research in recent years has shown that these compounds can be suitable as components of combined therapies with hyperbaric oxygenation. Such a combination increases the susceptibility of glioma tumour cells to cell death via apoptosis. Moreover, researchers planning on using any other antiglioma investigational pharmaceutics may want to consider using these agents in combination with CK2 inhibitors. However, different compounds are not equally effective when in such combination. More research is needed to elucidate the mechanism of treatment and optimize the treatment regimen. In addition, the role of CK2 in gliomagenesis and maintenance seems to have been challenged recently, as some compounds structurally similar to CK2 inhibitors do not inhibit CK2 while still being effective at reducing glioma viability and invasion. Furthermore, some newly developed inhibitors specific for CK2 do not appear to have strong anticancer properties. Further experimental and clinical studies of these inhibitors and combined therapies are warranted.

show abstract

“…Kinase inhibitors semaxanib and orantinib bear an oxindole moiety with a substituent at the C3 position [21]. Semaxanib has reached phase III clinical trials in the treatment of advanced colorectal cancer [22]; and orantinib is in phase II clinical trials for the treatment of breast cancer and in phase III clinical trials for the treatment of hepatocellular carcinoma [23].…”

Section: Introductionmentioning

confidence: 99%

Novel N-Substituted Amino Acid Hydrazone-Isatin Derivatives: Synthesis, Antioxidant Activity, and Anticancer Activity in 2D and 3D Models In Vitro

Tumosienė

Jonuškienė

Kantminienė

et al. 2021

IJMS

View full text Add to dashboard Cite

A series of novel mono and bishydrazones each bearing a 2-oxindole moiety along with substituted phenylaminopropanamide, pyrrolidin-2-one, benzimidazole, diphenylmethane, or diphenylamine fragments were synthesized, and their anticancer activities were tested by MTT assay against human melanoma A375 and colon adenocarcinoma HT-29 cell lines. In general, the synthesized compounds were more cytotoxic against HT-29 than A375. 3-((4-Methoxyphenyl)(3-oxo-3-(2-(2-oxoindolin-3-ylidene)hydrazinyl)propyl)amino)-N’-(2-oxoindolin-3-ylidene)propanehydrazide and (N’,N’’’)-1,1’-(methylenebis(4,1-phenylene))bis(5-oxo-N’-(2-oxoindolin-3-ylidene)pyrrolidine-3-carbohydrazide) were identified as the most active compounds against HT-29 in 2D and 3D cell cultures. The same compounds showed the highest antioxidant activity among the synthesized compounds screened by ferric reducing antioxidant power assay (FRAP). Their antioxidant activity is on par with that of a well-known antioxidant ascorbic acid.

show abstract

Drugs That Inhibit Signalling Pathways for Tumor Cell Growth and Proliferation

Cited by 15 publications

References 117 publications

Phosphoproteomic Analysis of Haemaphysalis longicornis Saliva Reveals the Influential Contributions of Phosphoproteins to Blood-Feeding Success

Phosphoproteomic Analysis of Haemaphysalis longicornis Saliva Reveals the Influential Contributions of Phosphoproteins to Blood-Feeding Success

Inhibiting CK2 among Promising Therapeutic Strategies for Gliomas and Several Other Neoplasms

Novel N-Substituted Amino Acid Hydrazone-Isatin Derivatives: Synthesis, Antioxidant Activity, and Anticancer Activity in 2D and 3D Models In Vitro

Contact Info

Product

Resources

About