Insights into the Uptake Mechanism of NrTP, A Cell-Penetrating Peptide Preferentially Targeting the Nucleolus of Tumour Cells
作者： Gandhi Rádis-Baptista , Beatriz G. de la Torre , David Andreu
DOI: 10.1111/J.1747-0285.2012.01377.X
关键词: Endocytosis 、 Homing (hematopoietic) 、 Cell cycle phase 、 Internalization 、 Cell biology 、 Biology 、 Cell 、 Nucleolus 、 Cell-penetrating peptide 、 Molecular biology 、 Receptor-mediated endocytosis
摘要: Nucleolar targeting peptides are 14-15 residue-long sequences designed by structural minimization of a snake toxin (J Med Chem 2008;50:7041). Peptides such as NrTP1 (YKQCHKKGGKK GSG) and analogues capable penetrating human cervix epithelial carcinoma cells homing into their nucleoli. We now show that similarly penetrates localizes in the nucleolus tumour derived from pancreatic (BxPC-3) ductal mammary gland (BT-474) carcinomas. Live cell confocal microscopy imaging, combined with flow cytometry analysis arrested to defined phases cycle, confirms uptake nucleolar independent cycle phase. Peptide is significantly reduced at low temperature. Also, drugs inhibiting chlatrin-mediated endocytosis severely decrease uptake, pointing clathrin-dependent route primary internalization mechanism. These results highlight not only novel efficient class cell-penetrating but also for exceptional ability target preferentially an essential dynamic subnuclear structure nucleolus.
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