The NFL-TBS.40-63 anti-glioblastoma peptide enters selectively in glioma cells by endocytosis

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• 作者：Claire L¨¦pinoux-Chambaud ; Jo?l Eyer
• 关键词：Antp ; antennapedia-homeodomain-derived antennapedia ; ATP ; adenosine triphosphate ; BSA ; bovine serum albumin ; chlorpr. ; chlorpromazine hydrochloride ; CPP ; cell penetrating peptide ; cytoch. D ; cytochalasin D ; DAPI ; 4&prime ; 6&prime ; -diamidino-2-phenylindole
• 刊名：International Journal of Pharmaceutics
• 出版年：2013
• 出版时间：1 October, 2013
• 年：2013
• 卷：454
• 期：2
• 页码：738-747
• 全文大小：2243 K

文摘

Glioblastoma are the most frequent and aggressive tumour of the nervous system despite surgical resection associated with chemotherapy and radiotherapy. Recently, we showed that the NFL-TBS.40-63 peptide corresponding to the sequence of a tubulin-binding site of neurofilaments, enters selectively in glioblastoma cells where it blocks microtubule polymerization, inhibits their proliferation, and reduces tumour development in rats bearing glioblastoma (). Here, we characterized the molecular mechanism responsible for the uptake of NFL-TBS.40-63 peptide by glioblastoma cells. Unlike other cell penetrating peptides (CPPs), which use a balance between endocytosis and direct translocation, the NFL-TBS.40-63 peptide is unable to translocate directly through the membrane when incubated with giant plasma membrane vesicles. Then, using a panel of markers and inhibitors, flow cytometry and confocal microscopy investigations showed that the uptake occurs mainly through endocytosis. Moreover, glycosaminoglycans and ¦ÁV¦Â3 integrins are not involved in the NFL-TBS.40-63 peptide recognition and internalization by glioblastoma cells. Finally, the signalling of tyrosine kinase receptors is involved in the peptide uptake, especially via EGFR overexpressed in tumour cells, indicating that the uptake of NFL-TBS.40-63 peptide by glioblastoma cells is related to their abnormally high proliferative activity.