Antimicrobial peptides of the Cecropin-family show potent antitumor activity against bladder cancer cells.
BACKGROUND
This study evaluated the cytotoxic and antiproliferative efficacy of two well-characterized members of the Cecropin-family of antimicrobial peptides against bladder tumor cells and benign fibroblasts.


METHODS
The antiproliferative and cytotoxic potential of the Cecropins A and B was quantified by colorimetric WST-1-, BrdU- and LDH-assays in four bladder cancer cell lines as well as in murine and human fibroblast cell lines. IC50 values were assessed by logarithmic extrapolation, representing the concentration at which cell viability was reduced by 50%. Scanning electron microscopy (SEM) was performed to visualize the morphological changes induced by Cecropin A and B in bladder tumor cells and fibroblasts.


RESULTS
Cecropin A and B inhibit bladder cancer cell proliferation and viability in a dose-dependent fashion. The average IC50 values of Cecropin A and B against all bladder cancer cell lines ranged between 73.29 mug/ml and 220.05 mug/ml. In contrast, benign fibroblasts were significantly less or not at all susceptible to Cecropin A and B. Both Cecropins induced an increase in LDH release from bladder tumor cells whereas benign fibroblasts were not affected. SEM demonstrated lethal membrane disruption in bladder cancer cells as opposed to fibroblasts.


CONCLUSIONS
Cecropin A and B exert selective cytotoxic and antiproliferative efficacy in bladder cancer cells while sparing targets of benign murine or human fibroblast origin. Both peptides may offer novel therapeutic strategies for the treatment of bladder cancer with limited cytotoxic effects on benign cells.
Suttmann
Henrik
H
Department of Urology and Pediatric Urology, Saarland University Hospital, Homburg/Saar, Germany. suttmann.urologikum@gmx.de
Retz
Margitta
M
Paulsen
Friedrich
F
Harder
Jürgen
J
Zwergel
Ulrike
U
Kamradt
Jörn
J
Wullich
Bernd
B
Unteregger
Gerhard
G
Stöckle
Michael
M
Lehmann
Jan
J
D000890:Anti-Infective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology* / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001973:Bromodeoxyuridine / Q000032:analysis; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D019476:Insect Proteins / Q000494:pharmacology* / Q000627:therapeutic use; D008855:Microscopy, Electron, Scanning; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000473:pathology* / Q000648:ultrastructure
D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D000970:Antineoplastic Agents; D019476:Insect Proteins; C031161:cecropin A; C031162:cecropin B protein, Insecta; D001973:Bromodeoxyuridine