Taurolidine–a new drug with anti-tumor and anti-angiogenic effects

Abstract

Taurolidine [bis(1,1-dioxoperhydro-1,2,4-thiadiazinyl-4)-methane (TRD)], a product derived from the aminosulfoacid taurin, was first described as an anti-bacterial substance. It was mainly used in the treatment of patients with peritonis as well as antiendoxic agent in patients with systematic inflammatory response syndrome. Meanwhile, quite interesting new experimental findings elucidated several new mechanisms concerning not only antibiotic but also anti-tumor effects. TRD significantly reduces the pathogenicity of prokaryotes, leading to a degeneration of the bacterial wall, and binds free lipoplysaccharides (LPSs) and exotoxins. Furthermore syntheses of tumor necrosis factor-a and interleukin-1b are reduced in LPS-stimulated human macrophages in a dose dependent manner. Tumor angiogenesis is promoted by enhanced expression of all these endogenous angiogenic factors, indicating an anti-angiogenetic effect of TRD. Tumor angiogenesis has a key role in tumor growth. TRD additionally inhibits tumor cell growth by a mitochondrial cytochrome c-dependent apoptotic mechanism, has a direct and elective effect on glial and neuronal brain tumor cells via Fas-ligand-mediated cell death, and inhibits protein synthesis at an early phase of translation, which might explain its various apoptotic effects. Subsequent to these experimental observations, TRD has shown encouraging clinical results after intravenous administration in patients with gastrointestinal malignancies and tumors of the central nerve system. A remarkable experimental observation that comes to complete the above-mentioned findings is the low toxicity on leukopoiesis and erythropoiesis as well as on kidney and liver function in animal models. Several other data confirm low toxicity of the agent after its clinical administration in humans. Prospective clinical studies are currently investigating the efficacy of TRD on local and metastatic tumor growth in different malignancies.

Efficacy of taurolidine against periodontopathic species—an in vitro study

“…A possible application is discussed in the treatment of tumors since it has been shown that taurolidine promotes apoptosis of tumor cells [12].…”

Taurolidine: A New Alternative Agent for the Management of the Postoperative Air Leak

“…11,18) The clinical application of TRD is an antiseptic. It has been used as an intraperitoneal antiseptic for the treatment and prevention of infection in contaminated surgery.…”

“…10) Recently, the anti-adherent effect of taurolidine in cancer cells was revealed. 11,12) There have been no reports on TRD pleurodesis. We have been used TRD for pleural space irrigation in patients with empyema and observed regional chest pain and faster air leak cessation after TRD irrigation in postoperative patients.…”

Taurolidine: Mode of administration in mouse tumor models

“…Taurolidine was well-tolerated, and encouraging initial results were reported in patients with pancreatic and stomach cancer, colo-rectal cancer and tumors of the central nervous system. [10][11][12] Yours sincerely, C. Braumann R. W. Pfirrmann…”