Antimicrobial peptides of the Cecropin-family show potent antitumor activity against bladder cancer cells

被引：119

作者：

Suttmann H. ^{[1
]}

Retz M. ^{[2
]}

Paulsen F. ^{[3
]}

Harder J. ^{[4
]}

Zwergel U. ^{[1
]}

Kamradt J. ^{[1
]}

Wullich B. ^{[1
]}

Unteregger G. ^{[1
]}

Stöckle M. ^{[1
]}

Lehmann J. ^{[1
]}

机构：

[1] Department of Urology and Pediatric Urology, Saarland University Hospital, Homburg/Saar

[2] Department of Urology, TU Rechts der Isar, München

[3] Department of Anatomy and Cell Biology, Martin-Luther-Universität Halle-Wittenberg

[4] Department of Dermatology, University Hospital Schleswig-Holstein, Campus Kiel

来源：

BMC Urology | / 8卷 / 1期

关键词：

Antimicrobial Peptide; Bladder Cancer Cell; Bladder Cancer Cell Line; Human Bladder Cancer Cell; Target Cell Membrane;

D O I：

10.1186/1471-2490-8-5

中图分类号：

学科分类号：

摘要：

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. IC 50 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 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. Conclusion. 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. © 2008 Suttmann et al; licensee BioMed Central Ltd.

引用

共 31 条

[1]

Jemal A., Murray T., Ward E., Samuels A., Tiwari R.C., Ghafoor A., Feuer E.J., Thun M.J., Cancer statistics, 2005, CA Cancer J Clin, 55, pp. 10-30, (2005)

[2]

Millan-Rodriguez F., Chechile-Toniolo G., Salvador-Bayarri J., Palou J., Algaba F., Vicente-Rodriguez J., Primary superficial bladder cancer risk groups according to progression, mortality and recurrence, J Urol, 164, pp. 680-684, (2000)

[3]

Oosterlinck W., Lobel B., Jakse G., Malmstrom P.U., Stockle M., Sternberg C.N., Guidelines on bladder cancer, Eur Urol, 41, pp. 105-112, (2002)

[4]

Herr H.W., Schwalb D.M., Zhang Z.F., Sogani P.C., Fair W.R., Whitmore Jr. W.F., Oettgen H.F., Intravesical bacillus Calmette-Guerin therapy prevents tumor progression and death from superficial bladder cancer: Ten-year follow-up of a prospective randomized trial., J Clin Oncol, 13, pp. 1404-1408, (1995)

[5]

Sylvester R.J., Van der Meijden A.P.M., Lamm D.L., Intravesical bacillus Calmette-Guerin reduces the risk of progression in patients with superficial bladder cancer: A meta-analysis of the published results of randomized clinical trials., J Urol, 168, pp. 1964-1970, (2002)

[6]

Lamm D.L., Blumenstein B.A., Crissman J.D., Montie J.E., Gottesman J.E., Lowe B.A., Sarosdy M.F., Bohl R.D., Grossman H.B., Beck T.M., Leimert J.T., Crawford E.D., Maintenance bacillus Calmette-Guerin immunotherapy for recurrent TA, T1 and carcinoma in situ transitional cell carcinoma of the bladder: A randomized Southwest Oncology Group Study, J Urol, 163, pp. 1124-1129, (2000)

[7]

Sylvester R.J., Van Der Meijden A.P., Witjes J.A., Kurth K., Bacillus calmette-guerin versus chemotherapy for the intravesical treatment of patients with carcinoma in situ of the bladder: A meta-analysis of the published results of randomized clinical trials, J Urol, 174, pp. 86-91, (2005)

[8]

Patard J.J., Rodriguez A., Lobel B., The current status of intravesical therapy for superficial bladder cancer, Curr Opin Urol, 13, pp. 357-362, (2003)

[9]

Sylvester R.J., Van der Meijden A.P.M., Oosterlinck W., Hoeltl W., Bono A.V., The side effects of Bacillus Calmette-Guerin in the treatment of Ta T1 bladder cancer do not predict its efficacy: Results from a European Organisation for Research and Treatment of Cancer Genito-Urinary Group Phase III Trial., Eur Urol, 44, pp. 423-428, (2003)

[10]

Boman H.G., Faye I., Gudmundsson G.H., Lee J.Y., Lidholm D.A., Cell-free immunity in Cecropia. a model system for antibacterial proteins, Eur J Biochem, 201, pp. 23-31, (1991)

← 1 2 3 4 →