Abstract

BackgroundThis 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.MethodsThe 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.ResultsCecropin 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 μg/ml and 220.05 μg/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.ConclusionCecropin 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.

Highlights

  • This study evaluated the cytotoxic and antiproliferative efficacy of two wellcharacterized members of the Cecropin-family of antimicrobial peptides against bladder tumor cells and benign fibroblasts

  • Recurrence and progression remain a serious threat to patients especially with high risk non-muscle invasive bladder cancers even if adjuvant intravesical treatment is performed according to existing guidelines with Bacillus Calmette-Guérin (BCG)-immunotherapy plus maintenance

  • Intravesical chemotherapy and BCG-immunotherapy are both associated with significant side effects

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Summary

Introduction

This study evaluated the cytotoxic and antiproliferative efficacy of two wellcharacterized members of the Cecropin-family of antimicrobial peptides against bladder tumor cells and benign fibroblasts. Postoperative adjuvant intravesical instillations of chemotherapeutic drugs such as mitomycin, doxorubicin or epirubicin as well as immunotherapy with Bacillus Calmette-Guérin (BCG) are established treatment options to reduce tumor recurrences [3,4,5]. Recurrence and progression remain a serious threat to patients especially with high risk non-muscle invasive bladder cancers even if adjuvant intravesical treatment is performed according to existing guidelines with BCG-immunotherapy plus maintenance. In this subgroup of patients, progression occurs in more than 15% of cases [3,5,6,7]. The identification of new potent intravesical agents is highly desirable to reduce toxicity and to improve longterm outcome

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