TRAIL and Taurolidine induce apoptosis and decrease proliferation in human fibrosarcoma

Daigeler, Adrien; Brenzel, Christina; Bulut, Daniel; Geisler, Anne; Hilgert, C.; Lehnhardt, Marcus; Steinau, Hans Ulrich; Flier, Annegret; Steinstraesser, Lars; Klein-Hitpaß, Ludger; Mittelkötter, U.; Uhl, Waldemar; Chromik, Ansgar M.

doi:10.1186/1756-9966-27-82

Cited by 22 publications

(33 citation statements)

References 67 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, once the disease has spread, the remaining treatment options are very limited. With up a maximum 30% response rate, treatment with established chemotherapeutic agents like doxorubicin and ifosfamide remain disappointing [24,25]. In this study, we have shown that EGCG induces cell cycle arrest and apoptosis through an intrinsic mitochondrial pathway in HT-1080 fibrosarcoma cells.…”

Section: Discussionmentioning

confidence: 65%

Apoptosis of human fibrosarcoma HT-1080 cells by epigallocatechin-3-O-gallate via induction of p53 and caspases as well as suppression of Bcl-2 and phosphorylated nuclear factor-κB

et al. 2010

View full text Add to dashboard Cite

Animal tumor bioassays and in vitro cell culture systems have demonstrated that epigallocatechin-3-O-gallate (EGCG), the predominant catechin in green tea, possesses anti-proliferative and pro-apoptotic effects on various cancer cells and tumors. In this study, we investigated the effects of EGCG on cell growth, cell cycle progression, and apoptosis in human fibrosarcoma HT-1080 cells. The involvement of p53, Bcl-2, Bax, caspases, and nuclear factor-κB (NF-κB) was examined as a mechanism for the anti-cancer activity of EGCG. Time-dependent intracellular trafficking of EGCG was also determined using fluorescein isothiocyanate (FITC)-conjugated EGCG (FITC-EGCG). Our data show that EGCG treatment caused dose-dependent cell growth inhibition, cell cycle arrest at the G(0)/G(1) phase, and DNA fragmentation suggesting the induction of apoptosis in HT-1080 cells. Immunoblot analysis revealed that the expression of p53, caspase-7 and -9 as well as the ratio of Bax/Bcl-2 protein increased significantly with higher EGCG concentrations and longer incubation times. Moreover, expression of phosphorylated NF-κB/p65 in HT-1080 cells was inhibited by EGCG treatment in a dose-dependent manner, while that of unphosphorylated NF-κB/p65 remained unaffected. Here we also reveal time-dependent internalization of FITC-EGCG into the cytosol of HT-1080 cells and its subsequent nuclear translocation. These results suggest that EGCG may interrupt exogenous signals directed towards genes involved in proliferation and cell cycle progression. Taken together, our data indicate that HT-1080 apoptosis may be mediated through the induction of p53 and caspases by the pro-oxidant activity of internalized EGCG, as well as suppression of Bcl-2 and phosphorylated NF-κB by the antioxidant activity of EGCG.

show abstract

Section: Discussionmentioning

confidence: 65%

Apoptosis of human fibrosarcoma HT-1080 cells by epigallocatechin-3-O-gallate via induction of p53 and caspases as well as suppression of Bcl-2 and phosphorylated nuclear factor-κB

et al. 2010

View full text Add to dashboard Cite

show abstract

“…In a previous experimental study, our group demonstrated that TRAIL and taurolidine synergistically induced apoptosis and inhibited cell proliferation of HT1080 fibrosarcoma cells in vitro (36). Inspired by these results, the present study treated human fibrosarcoma xenografts in athymic nude mice with TRAIL and taurolidine in order to evaluate the safety and antitumour efficacy of these two compounds.…”

Section: Discussionmentioning

confidence: 87%

“…In studies conducted in vitro, the combination of TRAIL and taurolidine was revealed to result in sustained cell death, and this was superior to single treatment with TRAIL or taurolidine, despite the lower concentrations of the two substances used in the combination trials (32,33,36). Experimental findings have also demonstrated that combined treatment with taurolidine may reduce the potential toxic side effects of TRAIL by reducing the required optimal dose of TRAIL, and by modulating its effector pathways without affecting the efficacy of its antitumour activity (33).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2016

Self Cite

View full text Add to dashboard Cite

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.

show abstract

“…RNA integrity was assessed using an Agilent 2100 Bioanalyzer (Agilent Technologies, Inc., Santa Clara, CA, USA). For microarray analyses, we applied the methods previously described by Daigeler et al (24). we used the affymetrix genechip platform, employing a standard protocol for sample preparation and microarray hybridisation.…”

Section: Methodsmentioning

confidence: 99%

Pro-apoptotic effects of pycnogenol on HT1080 human fibrosarcoma cells

Harati

Slodnik

Chromik

et al. 2015

International Journal of Oncology

Self Cite

View full text Add to dashboard Cite

Abstract. complete surgical resection with clear margins remains the mainstay of therapy for localised fibrosarcomas. Nevertheless, metastatic fibrosarcomas still represent a therapeutic dilemma. Commonly used chemotherapeutic agents like doxorubicin have proven to be effective in <30% of all cases of disseminated fibrosarcoma. Especially elderly patients with cardiac subdisease are not suitable for systemic chemotherapy with doxorubicin. Therefore we tested the apoptotic effects of the well-tolerated pine bark extract pycnogenol and its constituents on human fibrosarcoma cells (HT1080). Ten healthy subjects (six females, four males, mean age 24.8±6 years) received a single dose of 300 mg pycnogenol orally. Blood plasma samples were obtained before and 6 h after intake of pycnogenol. HT1080 cells were treated with these plasma samples. Additionally, HT1080 were incubated separately with catechin, epicatechin and taxifolin that are known as the main constituents of pycnogenol. Vital, apoptotic and necrotic cells were quantified using flow cytometric analysis. Gene expression was analyzed by RNA microarray. the results showed that single application of taxifolin, catechin and epicatechin reduced cell viability of HT1080 cells only moderately. A single dose of 300 mg pycnogenol given to 10 healthy adults produced plasma samples that led to significant apoptotic cell death ex vivo whereas pycnogenol-negative serum displayed no apoptotic activity. Microarray analysis revealed remarkable expression changes induced by pycnogenol in a variety of genes, which are involved in different apoptotic pathways of cancer cells [Janus kinase 1 (JAK1), DUSP1, RHOA, laminin γ1 (LAMC1), fibronectin 1 (FN1), catenin α1 (CTNNA1), ITGB1]. In conclusion, metabolised pycnogenol induces apoptosis in human fibrosarcoma cells. Pycnogenol exhibits its pro-apoptotic activity as a mixture and is more effective than its main constituents catechin, epicatechin and taxifolin indicating that the metabolised components interact synergistically. These results provide experimental support for in vivo trials assessing the effect of the pine bark extract pycnogenol.

show abstract

TRAIL and Taurolidine induce apoptosis and decrease proliferation in human fibrosarcoma

Abstract: Background: Disseminated soft tissue sarcoma still represents a therapeutic dilemma because effective cytostatics are missing. Therefore we tested TRAIL and Tarolidine (TRD), two substances with apoptogenic properties on human fibrosarcoma (HT1080).

Cited by 22 publications

References 67 publications

Apoptosis of human fibrosarcoma HT-1080 cells by epigallocatechin-3-O-gallate via induction of p53 and caspases as well as suppression of Bcl-2 and phosphorylated nuclear factor-κB

Apoptosis of human fibrosarcoma HT-1080 cells by epigallocatechin-3-O-gallate via induction of p53 and caspases as well as suppression of Bcl-2 and phosphorylated nuclear factor-κB

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

Pro-apoptotic effects of pycnogenol on HT1080 human fibrosarcoma cells

Contact Info

Product

Resources

About