Novel mode of action of polybia-MPI, a novel antimicrobial peptide, in multi-drug resistant leukemic cells.
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.
Wang
Kai-rong
KR
State Key Laboratory of Chinese Medicine and Molecular Pharmacology, Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hong Kong, China. wangkr04@gmail.com
Yan
Jie-xi
JX
Zhang
Bang-zhi
BZ
Song
Jing-jing
JJ
Jia
Peng-fei
PF
Wang
Rui
R
D000818:Animals; D017304:Annexin A5 / Q000378:metabolism; D000890:Anti-Infective Agents / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D016923:Cell Death / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D018432:Drug Resistance, Multiple / Q000187:drug effects; D005434:Flow Cytometry; D018922:HL-60 Cells / Q000187:drug effects; D006801:Humans; D019476:Insect Proteins / Q000494:pharmacology* / Q000627:therapeutic use*; D007939:Leukemia L1210 / Q000188:drug therapy; D051379:Mice; D009336:Necrosis; D010455:Peptides / Q000494:pharmacology / Q000627:therapeutic use; D014863:Wasps
D017304:Annexin A5; D000890:Anti-Infective Agents; D000970:Antineoplastic Agents; D019476:Insect Proteins; D010455:Peptides