Taurolidine--a new drug with anti-tumor and anti-angiogenic effects.
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.
Jacobi
Christoph A
CA
Department of General, Visceral, Vascular and Thoracic Surgery, Medical Faculty Charité, Humboldt University, Berlin, Germany. christoph.jacobi@charite.de
Menenakos
Charalambos
C
Braumann
Chris
C
D020533:Angiogenesis Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002986:Clinical Trials as Topic; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D023421:Models, Animal; D009369:Neoplasms / Q000098:blood supply / Q000188:drug therapy; D014176:Protein Biosynthesis / Q000187:drug effects; D013654:Taurine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use / Q000633:toxicity; D013829:Thiadiazines / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D016207:Cytokines; D013829:Thiadiazines; D042461:Vascular Endothelial Growth Factor A; D013654:Taurine; C012566:taurolidine