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Published in: Investigational New Drugs 4/2007

01-08-2007 | PRECLINICAL STUDIES

Taurolidine: a novel anti-neoplastic agent induces apoptosis of osteosarcoma cell lines

Authors: Denise K. Walters, Roman Muff, Bettina Langsam, Philipp Gruber, Walter Born, Bruno Fuchs

Published in: Investigational New Drugs | Issue 4/2007

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Summary

Taurolidine, the active agent of Taurolin®, is a broad spectrum anti-biotic that has been used for over 15 years for the treatment of severe surgical infections. Recently, taurolidine has been shown to possess anti-neoplastic properties in vitro and in vivo against a variety of cancers including ovarian, colon and prostate. In this study we assessed the cytotoxic activity of taurolidine against human osteosarcoma (OS) cell lines and normal human bone cells. Treatment with taurolidine inhibited the growth of all ten osteosarcoma cell lines tested and taurolidine was equally potent against cell lines with and without distinct genetic defects (i.e. p53, Rb). Moreover, taurolidine-induced growth inhibition was found to be associated with a dose dependent increase in the number of apoptotic cells and apoptosis was shown to be caspase-dependent. Taurolidine treatment was also found to inhibit adhesion of OS cell lines. Compared to OS cell lines, normal bone cells in primary culture were found to be less sensitive to the cytotoxic and anti-adhesive effects of taurolidine. These data indicate that taurolidine possesses potent anti-neoplastic activity against osteosarcoma cell lines and may have potential as a novel OS chemotherapeutic agent.
Literature
1.
go back to reference Friedman MA, Cater S (1972) The therapy of osteogenic sarcoma: current status and thoughts for the future. J Surg Oncol 4:482–510PubMedCrossRef Friedman MA, Cater S (1972) The therapy of osteogenic sarcoma: current status and thoughts for the future. J Surg Oncol 4:482–510PubMedCrossRef
2.
go back to reference Marina N, Gebhardt M, Teot L, Gorlick R (2004) Biology and therapeutic advances for pediatric osteosarcoma. Oncologist 9:422–441PubMedCrossRef Marina N, Gebhardt M, Teot L, Gorlick R (2004) Biology and therapeutic advances for pediatric osteosarcoma. Oncologist 9:422–441PubMedCrossRef
3.
go back to reference Browne MK, MacKenzie M, Doyle PJ (1978) Controlled trial of taurolidine in established bacterial peritonitis. Surg Gynecol Obstet 146:721–724PubMed Browne MK, MacKenzie M, Doyle PJ (1978) Controlled trial of taurolidine in established bacterial peritonitis. Surg Gynecol Obstet 146:721–724PubMed
4.
go back to reference Billing A, Frohlick D, Ruckdeschel G (1992) Der Einfluss von Taurolidine aud die korpereigene Abwehr und die Keimelimination bei der menschlichen Peritonitis. Langenbecks Arch Chir 377:180–185PubMed Billing A, Frohlick D, Ruckdeschel G (1992) Der Einfluss von Taurolidine aud die korpereigene Abwehr und die Keimelimination bei der menschlichen Peritonitis. Langenbecks Arch Chir 377:180–185PubMed
5.
go back to reference Bohm B, Schwenk W, Muller JM (1998) Long-term results after laparoscopic resection of colorectal carcinoma. Chirurg 70:453–455 Bohm B, Schwenk W, Muller JM (1998) Long-term results after laparoscopic resection of colorectal carcinoma. Chirurg 70:453–455
6.
go back to reference Knight BI, Skellern GG, Browne MK, Pfirrmann RW (1981) Peritoneal absorption of the antibacterial and antiendotoxin taurolidine in peritonitis. Br J Clin Pharmacol 12:695–699PubMed Knight BI, Skellern GG, Browne MK, Pfirrmann RW (1981) Peritoneal absorption of the antibacterial and antiendotoxin taurolidine in peritonitis. Br J Clin Pharmacol 12:695–699PubMed
7.
go back to reference Gidley MJ, Sanders JK, Myers ER, Allwood MC (1981) The mode of antibacterial action of some “masked” formaldehyde compounds. FEBS Lett 127:225–227PubMedCrossRef Gidley MJ, Sanders JK, Myers ER, Allwood MC (1981) The mode of antibacterial action of some “masked” formaldehyde compounds. FEBS Lett 127:225–227PubMedCrossRef
8.
go back to reference Gorman SP, McCafferty DF, Woolfson AD, Jones DS (1987) Electron and light microscope observations of bacterial cell surface effects due to taurolidine treatment. Lett Appl Microbiol 4:103–109 Gorman SP, McCafferty DF, Woolfson AD, Jones DS (1987) Electron and light microscope observations of bacterial cell surface effects due to taurolidine treatment. Lett Appl Microbiol 4:103–109
9.
go back to reference Gorman SP, McCafferty DF, Woolfson AD, Jones DS (1987) Reduced adherence of micro-organisms to human epithelial cells following treatment with Taurolidine, a novel antimicrobial agent. J Appl Bacteriol 62:315–320PubMed Gorman SP, McCafferty DF, Woolfson AD, Jones DS (1987) Reduced adherence of micro-organisms to human epithelial cells following treatment with Taurolidine, a novel antimicrobial agent. J Appl Bacteriol 62:315–320PubMed
10.
go back to reference Calabresi P, Goulette FA, Darnowski JW (2001) Taurolidine: cytotoxic and mechanistic evaluation of a novel anti-neoplastic agent. Cancer Res 61:6816–6821PubMed Calabresi P, Goulette FA, Darnowski JW (2001) Taurolidine: cytotoxic and mechanistic evaluation of a novel anti-neoplastic agent. Cancer Res 61:6816–6821PubMed
11.
go back to reference McCourt M, Wang JH, Sookhai S, Redmond HP (2000) Taurolidine inhibits tumor cell growth in vitro and in vivo. Ann Surg Oncol 7:685–691PubMedCrossRef McCourt M, Wang JH, Sookhai S, Redmond HP (2000) Taurolidine inhibits tumor cell growth in vitro and in vivo. Ann Surg Oncol 7:685–691PubMedCrossRef
12.
go back to reference Rodak R, Kubota H, Ishihara H, Eugster HP, Konu D, Mohler H, Yonekawa Y, Frei K (2005) Induction of reactive oxygen intermediates-dependent programmed cell death in human malignant ex vivo glioma cells and inhibition of the vacular endothelial growth factor production by taurolidine. J Neurosurg 102:1055–1068PubMedCrossRef Rodak R, Kubota H, Ishihara H, Eugster HP, Konu D, Mohler H, Yonekawa Y, Frei K (2005) Induction of reactive oxygen intermediates-dependent programmed cell death in human malignant ex vivo glioma cells and inhibition of the vacular endothelial growth factor production by taurolidine. J Neurosurg 102:1055–1068PubMedCrossRef
13.
go back to reference Shrayer DP, Lukoff H, King T, Calabresi P (2003) The effect of Taurolidine on adherent and floating subpopulations of melanoma cells. Anti-cancer Drugs 14:295–303PubMedCrossRef Shrayer DP, Lukoff H, King T, Calabresi P (2003) The effect of Taurolidine on adherent and floating subpopulations of melanoma cells. Anti-cancer Drugs 14:295–303PubMedCrossRef
14.
go back to reference Nici L, Monfils B, Calabresi P (2004) The effects of Taurolidine, a novel antineoplastic agent, on human malignant mesothelioma. Clin Cancer Res 10:7655–7661PubMedCrossRef Nici L, Monfils B, Calabresi P (2004) The effects of Taurolidine, a novel antineoplastic agent, on human malignant mesothelioma. Clin Cancer Res 10:7655–7661PubMedCrossRef
15.
go back to reference Stendel R, Picht T, Schilling A, Heidenreich J, Loddenkemper C, Janisch W, Brock M (2004) Treatment of glioblastoma with intravenous taurolidine. First clinical experience. Anticancer Res 24:1143–1147PubMed Stendel R, Picht T, Schilling A, Heidenreich J, Loddenkemper C, Janisch W, Brock M (2004) Treatment of glioblastoma with intravenous taurolidine. First clinical experience. Anticancer Res 24:1143–1147PubMed
16.
go back to reference Hellwinkel OJ, Muller J, Pollmann A, Kabisch H (2005) Osteosarcoma cell lines display variable individual reactions on wildtype p53 and Rb tumour-suppressor transgenes. J Gene Med 7:407–419PubMedCrossRef Hellwinkel OJ, Muller J, Pollmann A, Kabisch H (2005) Osteosarcoma cell lines display variable individual reactions on wildtype p53 and Rb tumour-suppressor transgenes. J Gene Med 7:407–419PubMedCrossRef
17.
go back to reference Boersma HH, Kietselaer B, Stolk L, Bennaghmouch A, Hofstra L, Narula J, Heidendal G, Reutelingsperger C (2005) Past, present, and future of Annexin A5: from protein discovery to clinical applications. J Nucl Med 46:2035–2050PubMed Boersma HH, Kietselaer B, Stolk L, Bennaghmouch A, Hofstra L, Narula J, Heidendal G, Reutelingsperger C (2005) Past, present, and future of Annexin A5: from protein discovery to clinical applications. J Nucl Med 46:2035–2050PubMed
18.
go back to reference Nestler G, Schulz U, Schubert D, Krüger S, Lippert H, Pross M (2005) Impact of taurolidine on the growth of CC531 coloncarcinoma cells in vitro and in a laparoscopic animal model in rats. Surg Endosc 19:280–284PubMedCrossRef Nestler G, Schulz U, Schubert D, Krüger S, Lippert H, Pross M (2005) Impact of taurolidine on the growth of CC531 coloncarcinoma cells in vitro and in a laparoscopic animal model in rats. Surg Endosc 19:280–284PubMedCrossRef
19.
go back to reference Conlan AA, Abramor E, Delikaris P, Hurwitz SS (1983) Taurolidine instillation as therapy for empyema thoracis. A prospective study of 50 patients. S Afr Med J 64:653–655PubMed Conlan AA, Abramor E, Delikaris P, Hurwitz SS (1983) Taurolidine instillation as therapy for empyema thoracis. A prospective study of 50 patients. S Afr Med J 64:653–655PubMed
20.
go back to reference Browne MK (1981) The treatment of peritonitis by an antiseptic—taurolin. Pharmatherapeutica 2:517–522PubMed Browne MK (1981) The treatment of peritonitis by an antiseptic—taurolin. Pharmatherapeutica 2:517–522PubMed
21.
go back to reference Buhler HU, Mikic S, Wicki O (1978) A new surgical lavage. Helv Chir Acta 45:143–145PubMed Buhler HU, Mikic S, Wicki O (1978) A new surgical lavage. Helv Chir Acta 45:143–145PubMed
22.
go back to reference Jacobi CA, Menenakos C, Braumann C (2005) Taurolidine—a new drug with anti-tumor and anti-angiogenic effects. Anti-cancer Drugs 16:917–921PubMedCrossRef Jacobi CA, Menenakos C, Braumann C (2005) Taurolidine—a new drug with anti-tumor and anti-angiogenic effects. Anti-cancer Drugs 16:917–921PubMedCrossRef
23.
go back to reference Darnowski J, Goulette FA, Cousens LP, Chatterjee D, Calabresi P (2004) Mechanistic and antineoplastic evaluation of taurolidine in the DU145 model of human prostate cancer. Cancer Chemother Pharmacol 54:249–258PubMedCrossRef Darnowski J, Goulette FA, Cousens LP, Chatterjee D, Calabresi P (2004) Mechanistic and antineoplastic evaluation of taurolidine in the DU145 model of human prostate cancer. Cancer Chemother Pharmacol 54:249–258PubMedCrossRef
24.
go back to reference Chambers AF, Groom AC, MacDonald IC (2002) Dissemination and growth of cancer cells in metastatic sites. Nat Rev Cancer 2:563–572PubMedCrossRef Chambers AF, Groom AC, MacDonald IC (2002) Dissemination and growth of cancer cells in metastatic sites. Nat Rev Cancer 2:563–572PubMedCrossRef
25.
go back to reference Link MP, Eilber F (1989) Pediatric oncology: osteosarcoma. In: Pizzo PS, Poplack DG (eds) Principles and practice of pediatric oncology. Lippincott, Philadelphia, pp 689–711 Link MP, Eilber F (1989) Pediatric oncology: osteosarcoma. In: Pizzo PS, Poplack DG (eds) Principles and practice of pediatric oncology. Lippincott, Philadelphia, pp 689–711
26.
Metadata
Title
Taurolidine: a novel anti-neoplastic agent induces apoptosis of osteosarcoma cell lines
Authors
Denise K. Walters
Roman Muff
Bettina Langsam
Philipp Gruber
Walter Born
Bruno Fuchs
Publication date
01-08-2007
Published in
Investigational New Drugs / Issue 4/2007
Print ISSN: 0167-6997
Electronic ISSN: 1573-0646
DOI
https://doi.org/10.1007/s10637-007-9052-9

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