Potent synergy of dual antitumor peptides for growth suppression of human glioblastoma cell lines

Abstract

Molecular targeting agents have become formidable anticancer weapons, which show much promise against the refractory tumors. Functional peptides are among the more desirable of these nanobio-tools. Intracellular delivery of multiple functional peptides forms a basis for potent, non-invasive mode of delivery, providing distinctive therapeutic advantages. Here, we examine growth suppression efficiency of human glioblastomas by dualpeptide targeting.

Tumour lineage-homing cell-penetrating peptides as anticancer molecular delivery systems

“…In total 10,000 cells were examined in each sample (FACScan, Becton Dickinson, USA). Cell cycle analysis was also performed by FACScan, using propidium iodide staining 20,21 .…”

“…S4a). Antitumour peptides were designed by fusing CPP44 or CPP2, as cellpenetrating domains, to the minimal inhibitory sequence of p16 (p16MIS) that has been reported to restore lost p16 function via GPG sequence [19][20][21] (Fig. 4b).…”

A new molecular targeted therapeutic approach for renal cell carcinoma with a p16 functional peptide using a novel transporter system

“…this transporter, wr-T, consisted of tryptophan-rich domains (serving as a cargo to attach functional peptides) fused with nine D-arginines serving as a PTD. They reported that the wr-T system provided higher delivery efficiency than Pep-1 (whose delivery efficiency is already reported) and achieved an antitumor effect by delivering antitumor peptides to leukemia, lymphoma and glioma cells (21)(22)(23). In the present study, we delivered antitumor peptides to renal cell carcinoma cell lines using a similar system, and evaluated their antitumor effect.…”

“…peptide purity was >95%. the amino acid sequence of the Wr-t transporter is: KetWWetWWteWWteWsQ GPGrrrrrrrrr (r, D-enantiomer arginine) (21,22). For the synthesis of p16 MIs, the 10 sequential amino acid residue sequence 'FlDTlVVlHR', identified as the mIs of p16 by Fahraeus et al (24), was defined as the functional core of the peptide, which is insoluble, as is the entire p16 molecule (mIs hydrophobicity, 69.2%).…”

“…PTDs, being able to pass through the cell membrane of living cells, are considered useful for intracellular delivery of functional proteins or peptides targeting intracellular molecules, and many PTDs, including HIV-1 TAT, pAntp43-58 and polyarginine (R4-16), have been reported (13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23). In 1998, Nagahara et al produced a recombinant protein (TAT-p27 kip1 fusion protein), transduced it into cells, and induced G1 arrest and cell migration (16).…”