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The influence of Tat-derived peptide (Tat-LK15) on the uptake of membrane p- glycoproteins substrate (Calcein AM) | ||
| Iraqi Journal of Pharmacy | ||
| Article 1, Volume 16, Issue 1, 2019, Pages 1-21 PDF (371.05 K) | ||
| Document Type: Research Paper | ||
| DOI: 10.33899/iphr.2019.165706 | ||
| Authors | ||
| Myasar Alkotaji* 1; Alain Pluen2; Harmesh Aojula2 | ||
| 1College of Pharmacy, University of Mosul, Mosul, Iraq | ||
| 2School of pharmacy, University of Manchester, Manchester, UK | ||
| Abstract | ||
| Introduction: Cell penetrating peptides (CPPs) have been used in many areas of drug delivery for mediating the delivery of peptides, protein, DNA, siRNA and liposomes. Additionally they have shown an ability to overcome drug resistance in cells and enhancing chemotherapeutic activity. Our group has recently designed a promising multifunctional peptide, Tat-LK15, originating from the fusion of Tat peptide (49-57) with the synthetic amphipathic (membrane lytic) peptide, LK15. To date, Tat-LK15 peptide’s effect on the cell membrane has not been assessed. Objective: The aim of this work is to study the influence of Tat-LK15 peptide on the uptake of p-glycoproteins substrate (Calcein AM). This could explain the effect of peptide on membrane. Also this work aimed to explore whether the peptide characteristics could be exploited to improve the delivery of the cytotoxic agent, doxorubicin to doxorubicin resistant cells. Results and discussions: Flow cytometry experiments revealed that Tat-LK15 peptide was not able to overcome multidrug resistance or to reverse the reduced uptake of Ca AM in the doxorubicin resistance sublines (HT29dx and K562dx). In contrast, Tat-LK15 peptide exhibited an inhibitory effect on the calcein fluorescence in both K562 and HT29 cell lines and their doxorubicin resistance sublines (HT29dx and K562dx). The supposed mechanism assumed that Tat-LK15 peptide may change phospholipid architecture/packing in the cell membrane leading to a reduction in the cell membrane permeability to the entry of Ca AM. Interestingly, this study indicates the possible membrane activity of Tat-LK15 peptide, which was confirmed in another work. | ||
| Keywords | ||
| Tat-LK15 peptide; p-glycoprotein substrate; cytotoxic agent; drug delivery | ||
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