Novel mode of action of polybia-MPI, a novel antimicrobial peptide, in multi-drug resistant leukemic cells.

Abstract:

:As the frequent emergency of resistant tumor cells during treatment, the development of new agents with new modes of action attracts a great deal of interest. Polybia-MPI was a short cationic alpha-helical amphiphilic peptide that has selective toxicity toward cancer cells but no hemolytic activity. Its target selectivity is based on the binding preference to membranes containing anionic phospholipids by electrostatic driving. Its ability to make PI and trypan blue permeate into tumor cells at the same rate (within minutes), suggests a killing mechanism that involves plasma membrane perturbation. SEM and confocal microscopy experiments verified that the cell died as a result of acute injury and bursting, suggesting necrosis. As compared to the conventional chemotherapy, polybia-MPI targets at the cell membrane rather than enters into the cell to exert its action. So it is difficult for tumor cells to develop resistance to polybia-MPI during treatment and its action is not affected by the common multi-drug resistant mechanism. Although this is an initial study that looked at its in vitro activity rather than the in vivo activity, with the increasing resistance of conventional chemotherapy, polybia-MPI may offer a novel therapeutic strategy in the treatment of multi-drug resistant cancer.

journal_name

Cancer Lett

journal_title

Cancer letters

authors

Wang KR,Yan JX,Zhang BZ,Song JJ,Jia PF,Wang R

doi

10.1016/j.canlet.2008.12.027

subject

Has Abstract

pub_date

2009-06-08 00:00:00

pages

65-72

issue

1

eissn

0304-3835

issn

1872-7980

pii

S0304-3835(08)00979-8

journal_volume

278

pub_type

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