Comparative analysis of cell death induction by Taurolidine in different malignant human cancer cell lines

Chromik, Ansgar M.; Daigeler, Adrien; Bulut, Daniel; Flier, Annegret; May, Christina E.; Harati, Kamran; Roschinsky, Jan; Sülberg, D.; Ritter, Peter R.; Mittelkötter, U.; Hahn, Stephan A.; Uhl, Waldemar

doi:10.1186/1756-9966-29-21

Cited by 20 publications

(31 citation statements)

References 35 publications

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“…Opposite to this, in PancTuI cells treated with 1500 μmol/l the amount of apoptotic cells prevailed. This dose depending ratio of viable, apoptotic and necrotic cells is according to previous studies with TRD in our group [15] and by others [13, 26]. Regarding the pronounced necrotic effect of rising concentrations of substance 2250, only speculations are possible.…”

Section: Discussionsupporting

confidence: 81%

“…This anti-neoplastic and apoptosis inducing effect could also be verified by other research groups [11] in a variety of cell lines derived from malignant tumors e.g. glioblastoma [12], melanoma [13], mesothelioma [14] and colon carcinoma [15]. Furthermore, latest reports about the systemic application of TRD in patients with gastric carcinoma and glioblastoma revealed promising results with almost absence of toxicity [16, 17].…”

Section: Introductionsupporting

confidence: 62%

“…Previous studies with TRD revealed an involvement of ROS 12, 40 [29], triggering apoptosis via caspase-independent pathways [12, 20], caspase-dependent pathways 40 [15, 20, 25] as well as necroptosis and autophagy [26]. Furthermore, cell death, induced by ROS, has been shown to be prevented by applying the radical scavenger N-acetycysteine (NAC) [12, 25, 29].…”

Section: Discussionmentioning

confidence: 99%

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Innovative substance 2250 as a highly promising anti-neoplastic agent in malignant pancreatic carcinoma - in vitro and in vivo

et al. 2017

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BackgroundFormer studies already revealed the anti-neoplastic properties of the anti-infective agent Taurolidine (TRD) against many tumor species in vitro and in vivo. Its anti-proliferative and cell death inducing capacity is largely due to its main derivative Taurultam (TRLT). In this study it could be demonstrated, that substance 2250 - a newly defined innovative structural analogue of TRLT - exhibits an anti-neoplastic effect on malignant pancreatic carcinoma in vitro and in vivo.MethodsThe anti-neoplastic potential of substance 2250 as well as its mode of action was demonstrated in extensive in vitro analysis, followed by successful and effective in vivo testings, using xenograft models derived from established pancreatic cancer cell lines as well as patient derived tissue.ResultsOur functional analysis regarding the role of oxidative stress (ROS) and caspase activated apoptosis showed, that ROS driven programmed cell death (PCD) is the major mechanisms induced by substance 2250 in pancreatic carcinoma. What is strongly relevant towards clinical practice is especially the observed inhibition of patient derived pancreatic cancer tumor growth in mice treated with this new substance in combination with its sharply higher metabolic stability.ConclusionThese encouraging results provide new therapeutical opportunities in pancreatic cancer treatment and build the basis for further functional analysis as well as first clinical studies for this promising agent.

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Section: Discussionsupporting

confidence: 81%

Section: Introductionsupporting

confidence: 62%

Section: Discussionmentioning

confidence: 99%

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Innovative substance 2250 as a highly promising anti-neoplastic agent in malignant pancreatic carcinoma - in vitro and in vivo

et al. 2017

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“…For grampositive bacteria and fungi, which do not display fimbriae proteins, they propose that hydrolysis products could induce reactivity and imply a more general mechanism of action. Moreover, recent studies have found antineoplastic activity and discuss its role in cancer treatment [31,32].…”

Section: Introductionmentioning

confidence: 99%

Antibacterial effect of taurolidine (2%) on established dental plaque biofilm

2011

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Preliminary data have suggested that taurolidine may bear promising disinfectant properties for the therapy of bacterial infections. However, at present, the potential antibacterial effect of taurolidine on the supragingival plaque biofilm is unknown. To evaluate the antibacterial effect of taurolidine on the supragingival plaque biofilm using the vital fluorescence technique and to compare it with the effect of NaCl and chlorhexidine (CHX), 18 subjects had to refrain from all mechanical and chemical hygiene measures for 24 h. A voluminous supragingival plaque sample was taken from the buccal surfaces of the lower molars and wiped on an objective slide. The sample was then divided into three equal parts and mounted with one of the three test or control preparations (a) NaCl, (b) taurolidine 2% and (c) CHX 0.2%. After a reaction time of 2 min, the test solutions were sucked of. Subsequently, the plaque biofilm was stained with fluorescence dye and vitality of the plaque flora was evaluated under the fluorescence microscope (VF%). Plaque samples treated with NaCl showed a mean VF of 82.42 ± 6.04%. Taurolidine affected mean VF with 47.57 ± 16.60% significantly (p < 0.001, paired t test). The positive control CHX showed the lowest mean VF values (34.41 ± 14.79%; p < 0.001 compared to NaCl, p = 0.017 compared to taurolidine). Taurolidine possesses a significant antibacterial effect on the supragingival plaque biofilm which was, however, not as pronounced as that of CHX.

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“…Taurolidine, an antiseptic agent derived from the amino acid taurine, has been utilized for the treatment of peritonitis and catheter-related infections (22). Additionally, studies have demonstrated that taurolidine may be used effectively to treat certain malignant diseases (23)(24)(25)(26).…”

Section: Introductionmentioning

confidence: 99%

Evaluation of the safety and efficacy of TRAIL and taurolidine use on human fibrosarcoma xenografts in vivo

et al. 2016

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Abstract. Fibrosarcomas are rare malignant soft tissue tumours that exhibit a poor response to current therapeutic regimens. Previously, tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) and taurolidine were observed to induce apoptosis synergistically in HT1080 human fibrosarcoma cells in vitro. Consequently, the present study aimed to assess the safety and efficacy of TRAIL in combination with taurolidine on the local growth of fibrosarcoma xenografts in vivo. HT1080 fibrosarcoma cells were inoculated subcutaneously into both flanks of 49 athymic nude mice in order to establish tumour xenografts. TRAIL and taurolidine were applied intraperitoneally at various single and cumulative treatment doses. After 12 days, the experiment was terminated and surviving animals were euthanised. Tumour progression was determined during and following treatment. To assess the potential toxic effects of the two compounds, the organs (lung, liver, kidney and heart) of all animals were examined histologically. The results revealed that combined treatment with TRAIL and taurolidine significantly inhibited the growth of HT1080 xenografts, whereas untreated animals had steadily increasing tumours. The most effective combination was TRAIL at 2 µg per application (cumulative dose, 16 µg) and taurolidine at 30/15 mg per application (cumulative dose, 180 mg), reducing the mean size of implanted xenografts to 10.9 mm 2 following treatment (vs. 48.9 mm 2 in the control group; P=0.0100). Despite distinct tumour mass reduction, the rate of mortality was significantly increased in animals treated with TRAIL and taurolidine in a taurolidine dose-dependent manner; however, histological examinations of relevant organs revealed no evidence of systemic toxicity (mean survival time, 7.9 days in the treated groups vs. 12 days in the control group; P<0.0010). In summary, whilst the combination of TRAIL and taurolidine synergistically inhibited the growth of fibrosarcoma xenografts in vivo, it was also accompanied by significantly increased mortality rate. Thus, although taurolidine is assumed to be a compound with an acceptable toxicity profile, and therefore increasingly used in clinical trials, the current findings raise concerns with regard to its safety and therapeutic index, and indicate the requirement for further detailed toxicity tests.

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Comparative analysis of cell death induction by Taurolidine in different malignant human cancer cell lines

Cited by 20 publications

References 35 publications

Innovative substance 2250 as a highly promising anti-neoplastic agent in malignant pancreatic carcinoma - in vitro and in vivo

Innovative substance 2250 as a highly promising anti-neoplastic agent in malignant pancreatic carcinoma - in vitro and in vivo

Antibacterial effect of taurolidine (2%) on established dental plaque biofilm

Evaluation of the safety and efficacy of TRAIL and taurolidine use on human fibrosarcoma xenografts in vivo

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