Membrane disrupting lytic peptides for cancer treatments.
Membrane disrupting lytic peptides are abundant in nature and serve insects, invertebrates, vertebrates and humans as defense molecules. Initially, these peptides attracted attention as antimicrobial agents; later, the sensitivity of tumor cells to lytic peptides was discovered. In the last decade intensive research has been conducted to determine how lytic peptides lyse bacteria and tumor cells. A number of synthetic peptides have been designed to optimize their antibiotic and anti-tumor properties and improve their therapeutic capabilities. The sequences of alpha-helical cationic membrane disrupting peptides has been discussed, their proposed mechanisms of action reviewed, and their roles in cell selectivity and tumor cell destruction considered. Parameters important for the selection and design of lytic peptides for cancer treatments include increased activities against tumor cells, low cytolytic activities to normal mammalian cells and erythrocytes. The conjugation of lytic peptides with hormone ligands and the production of pro-peptides provide methods for targeting of cancer cells. The therapeutic possibilities in cancer treatment by targeted lytic peptides are broad and offer improvement to currently used chemotherapeutical drugs. Lytic peptides interact with the tumor cell membrane within minutes, and their activity is independent of multi-drug resistance. Lytic peptide-chorionic gonadotropin (CG) conjugates destroy primary tumors, prevent metastases and kill dormant and metastatic tumor cells. These conjugates do not destroy vital organs; they are not antigenic, and are more toxic to tumor cells than to non-malignant cells.
Pennington Biomedical Research Center, LSU, Baton Rouge, LA 70808, USA. Leuschc@pbrc.edu
Carola
C
Leuschner
William
W
Hansel
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D002462:Cell Membrane / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D009369:Neoplasms / Q000188:drug therapy* / Q000648:ultrastructure; D010455:Peptides / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D011487:Protein Conformation
D000970:Antineoplastic Agents; D010455:Peptides