Effects of cell penetrating Notch inhibitory peptide conjugated to elastin-like polypeptide on glioblastoma cells

Autor:	Jung Su Ryu, Teuta Opačak-Bernardi, Drazen Raucher
Rok vydání:	2017
Předmět:	0301 basic medicine Cell cycle checkpoint Cell Notch signaling pathway Pharmaceutical Science Apoptosis Cell-Penetrating Peptides Biology 03 medical and health sciences Drug Delivery Systems 0302 clinical medicine Cell Line Tumor medicine Humans Cytotoxicity Receptors Notch Brain Neoplasms Cell Cycle Checkpoints Hyperthermia Induced Molecular biology Cell penetrating peptide Notch pathway dnMAML anticancer elastin-like polypeptide Elastin Cell biology DNA-Binding Proteins 030104 developmental biology medicine.anatomical_structure Blood-Brain Barrier 030220 oncology & carcinogenesis Cancer cell Cell-penetrating peptide biology.protein Glioblastoma Peptides Transcription Factors
Zdroj:	Journal of Drug Targeting. 25:523-531
ISSN:	1029-2330 1061-186X
Popis:	Notch pathway was found to be activated in most glioblastomas (GBMs), underlining the importance of Notch in formation and recurrence of GBM. In this study, a Notch inhibitory peptide, dominant negative MAML (dnMAML), was conjugated to elastin-like polypeptide (ELP) for tumor targeted delivery. ELP is a thermally responsive polypeptide that can be actively and passively targeted to the tumor site by localized application of hyperthermia. This complex was further modified with the addition of a cell penetrating peptide, SynB1, for improved cellular uptake and blood–brain barrier penetration. The SynB1–ELP1–dnMAML was examined for its cellular uptake, cytotoxicity, apoptosis, cell cycle inhibition and the inhibition of target genes’ expression. SynB1–ELP1–dnMAML inhibited the growth of D54 and U251 cells by inducing apoptosis and cell cycle arrest, especially in the presence of hyperthermia. Hyperthermia increased overall uptake of the polypeptide by the cells and enhanced the resulting pharmacological effects of dnMAML, showing the inhibition of targets of Notch pathway such as Hes-1 and Hey-L. These results confirm that dnMAML is an effective Notch inhibitor and combination with ELP may allow thermal targeting of the SynB1–ELP1–dnMAML complex in cancer cells while avoiding the dangers of systemic Notch inhibition.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fc8ce841fff6b0f5e704dbbe934e4eb0 https://doi.org/10.1080/1061186x.2017.1289537 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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