Oligopeptides derived from autophosphorylation sites of EGF receptor suppress EGF-stimulated responses in human lung carcinoma A549 cells

Kuroda, Yoshihiro; Kato-Kogoe, Nahoko; Tasaki, Emi; Murata, Eri; Ueda, Koyo; Abe, Mineo; Miyamoto, Kazuhide; Nakase, Ikuhiko; Futaki, Shiroh; Tohyama, Yumi; Hirose, Munetaka

doi:10.1016/j.ejphar.2012.10.007

Cited by 9 publications

(6 citation statements)

References 29 publications

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“…There is evidence that many synthetic oligopeptides modified from the extended C-terminal segment of EGFR suppress phosphorylation of purified EGFR-TK by either non-ATPcompetitive or ATP-competitive mechanisms (Abe et al, 2008). Those peptides also have a potential to inhibit the proliferation and anti-apoptotic effect of the NSCLC cell line (Kuroda et al, 2013). We have recently utilized the computational drug design approach combined with in vitro experiments to identify the tripeptides that have a promising inhibitory activity against HER2-TK (Seetaha et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

“…cytotoxicity, EGFR-TK, IC 50 , inhibitory activity, intermolecular interaction, kinase inhibitor, molecular dynamics simulation, relative binding free energy, tripeptide biomimicking has been reported as a novel strategy to emulate an existing molecule with a more powerful element for improving its efficacy (Ju et al, 2018). Small peptides are a class of biomolecules that have come to be used to overcome multiple obstacles confronting those chemicalbased inhibitors (Abe et al, 2008;Kuroda et al, 2013). Our previous work with molecular docking-based virtual screening followed by molecular dynamic simulations on tripeptides against the human epithelial growth factor receptor 2 tyrosine kinase domain (HER2-TK) demonstrated that the tripeptides, WWW and FYW, elicited a promising capacity similar to lapatinib in terms of binding avidity (Seetaha et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

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Identification of tripeptides against tyrosine kinase domain of EGFR for lung cancer cell inhibition by in silico and in vitro studies

et al. 2021

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Epidermal growth factor receptor tyrosine kinase domain (EGFR-TK) has been one of the prominent targets for therapeutics of several human cancers, in particular non-small cell lung cancer. Although several small chemical compounds targeting EGFR-TK have been approved by FDA for treatment of such a cancer, the discovery of a new class of EGFR-TK inhibitors, for example, small peptides, is still desired. In this study, using molecular docking-based virtual screening, we selected five small peptides with high docking scores from eight thousand peptides as candidate compounds against EGFR-TK. Among five, the tripeptide WFF had the most potency to suppress the survival of non-small cell lung cancer cells but had the least toxicity to human liver cancer cells. Our in vitro kinase assays showed that WFF exhibited much lower inhibitory activity against purified EGFR-TK than the drug erlotinib (i.e., IC 50 values of ≈ 0.62 μM vs ≈ 7.57 nM, respectively). The relative free binding energies estimated from molecular dynamic simulations were consistent with the in vitro experiments in which the WFF bound had a lower affinity than erlotinib bound to EGFR-TK (i.e., ΔG bind values of −20.3 kJ/mol vs ≈ −126.8 kJ/mol, respectively). In addition, the simulation analyses demonstrated the difference in EGFR binding preference between the drug and tripeptide in which erlotinib was stably bound in the ATP-binding pocket for 4-anilinoquinazoline class of inhibitors, while WFF moved out of that pocket to interact with polar amino acid residues on the αC-helix, activation loop,

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Identification of tripeptides against tyrosine kinase domain of EGFR for lung cancer cell inhibition by in silico and in vitro studies

et al. 2021

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“…The increased level of penetration of PLHSpT led to an enhanced apoptosis rate and a several times higher Caspase-3 level. In another trial, the TAT peptide (YGRKKRRQRRR) was fused with Ac-ENAEYLR and Ac-NYQQN peptides that lower the phosphorylation level of the pure EGF receptor (Kuroda et al, 2013). The TAT-NYQQN fusion led to a higher activity level of Caspase-3 in A549 cells.…”

Section: Tat Peptidesmentioning

confidence: 99%

Cell penetrating peptides: Highlighting points in cancer therapy

Asrorov

Wang

Zhang

et al. 2023

Drug Development Research

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Cell‐penetrating peptides (CPPs), first identified in HIV a few decades ago, deserved great attention in the last two decades; especially to support the penetration of anticancer drug means. In the drug delivery discipline, they have been involved in various approaches from mixing with hydrophobic drugs to the use of genetically conjugated proteins. The early classification as cationic and amphipathic CPPs has been extended to a few more classes such as hydrophobic and cyclic CPPs so far. Developing potential sequences utilized almost all methods of modern science: choosing high‐efficiency peptides from natural protein sequences, sequence‐based comparison, amino acid substitution, obtaining chemical and/or genetic conjugations, in silico approaches, in vitro analysis, animal experiments, etc. The bottleneck effect in this discipline reveals the complications that modern science faces in drug delivery research. Most CPP‐based drug delivery systems (DDSs) efficiently inhibited tumor volume and weight in mice, but only in rare cases reduced their levels and continued further processes. The integration of chemical synthesis into the development of CPPs made a significant contribution and even reached the clinical stage as a diagnostic tool. But constrained efforts still face serious problems in overcoming biobarriers to reach further achievements. In this work, we reviewed the roles of CPPs in anticancer drug delivery, focusing on their amino acid composition and sequences. As the most suitable point, we relied on significant changes in tumor volume in mice resulting from CPPs. We provide a review of individual CPPs and/or their derivatives in a separate subsection.

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“…27 TAT demonstrates a high degree of biocompatibility with no compromise in cell viability of A549 even at high concentrations of 1 mM. 40 TAT uses a non-endocytic, direct translocation mechanism that allows it to penetrate the lipid bilayer of the cell membrane without causing significant membrane damage 27,41 and is not involved in processes directly regulating intracellular radicals. Therefore, TAT has been selected as a potential negative control.…”

Section: Bioactive Ligands Sst Tpp and Tatmentioning

confidence: 99%

Nanoscale detection and real-time monitoring of free radicals in a single living cell under the stimulation of targeting moieties using a nanodiamond quantum sensor

Wu,

Lu,

Sow

et al. 2023

Preprint

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Intracellular radicals play important roles in cell signaling and regulation of growth factors, cytokines, transcription, apoptosis, and immunomodulation, among others. To gain a more comprehensive understanding of their biological functions in a spatio-temporal perspective, there is a great need for nanoscale sensitive tools that allow real-timeiin detection of these reactive species. Currently, intracellular radical probes are based on chemical reactions that could significantly alter radical levels during detection. Due to the excellent biocompatibility and favorable photophysical properties of nitrogen-vacancy (NV‒) centers in fluorescent nanodiamonds (fNDs), the fNDs can serve as a powerful and chemically inert nanotool for intracellular radical detection. In this study, a positively charged nanogel (NG) coating was prepared to prevent the precipitation of fNDs and promote cellular internalization. After internalization of nanodiamond-nanogels (fND-NGs), different stimulators, namely somatostatin (SST), triphenylphosphonium (TPP), and trans-activator of transcription (TAT) peptide, which are widely used cell- or organelle- targeting ligands in medicine, drug delivery, and diagnostics, were applied to stimulate the cells. In parallel, the intracellular radical changes under stimulation of SST, TPP, and TAT ligands were monitored by fND-NGs in a home-built ODMR microscope. Our method allows for detecting intracellular radicals in-situ and monitoring their real-time changes during incubation with the targeting ligands in a single living cell. We believe that our method will provide insights into the generation of radical stress in cells, which could improve our fundamental understanding of the pharmacology and signaling pathways of widely used cell- and organelle-targeting ligands associated with free radicals.

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Oligopeptides derived from autophosphorylation sites of EGF receptor suppress EGF-stimulated responses in human lung carcinoma A549 cells

Cited by 9 publications

References 29 publications

Identification of tripeptides against tyrosine kinase domain of EGFR for lung cancer cell inhibition by in silico and in vitro studies

Identification of tripeptides against tyrosine kinase domain of EGFR for lung cancer cell inhibition by in silico and in vitro studies

Cell penetrating peptides: Highlighting points in cancer therapy

Nanoscale detection and real-time monitoring of free radicals in a single living cell under the stimulation of targeting moieties using a nanodiamond quantum sensor

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