The antibacterial substance taurolidine exhibits anti-neoplastic action based on a mixed type of programmed cell death

Stendel, Ruediger; Biefer, Héctor Rodriguez Cetina; Dékány, Gabriela Marta; Kubota, Hisashi; Münz, Christian; Wang, Sheng; Möhler, Hanns; Yonekawa, Yasuhiro; Frei, Karl

doi:10.4161/auto.5.2.7404

Cited by 22 publications

(45 citation statements)

References 39 publications

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“…This has recently also been described in the caspase-independent cell death of glioblastoma cell lines incubated with taurolidine. 50 Moreover, ongoing processing of caspase 3 in the presence of Z-VAD has been described before in B cells after B-cell receptor triggering and interestingly also after treatment with the ROS-inducing agent CCCP. 30 Second, the rapid kinetics of rituximab-induced cell death in CLL cells (within hours) is certainly not characteristic for classical apoptosis.…”

Section: Discussionmentioning

confidence: 84%

CD40 stimulation sensitizes CLL cells to rituximab-induced cell death

et al. 2011

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In vitro CD40-stimulated chronic lymphocytic leukemia (CLL) cells are resistant to cytotoxic drugs. In sharp contrast, we here show that CD40 stimulation sensitizes CLL cells to rituximabmediated cell death. This increased sensitivity is specific for anti-CD20 treatment. Rituximab-mediated death in CD40-stimulated CLL cells shows rapid kinetics (within hours), and is caspase and p53 independent, but depends on extracellular Ca 2 þ and reactive oxygen species (ROS) production. By increasing basal ROS production, CD40 stimulation sensitizes CLL cells to rituximab-mediated death. Our findings provide a rationale for combination treatment of CLL with cytotoxic drugs and anti-CD20 monoclonal antibodies.

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Section: Discussionmentioning

confidence: 84%

CD40 stimulation sensitizes CLL cells to rituximab-induced cell death

et al. 2011

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“…Taurolidine potently prevented cell proliferation (EC 50 , 1 to 7 μg/ml) as shown for glioma cell lines (19–21) as well as ex vivo human glioblastoma cells (19). In addition, at higher concentrations, Taurolidine induced acute cytotoxicity (EC 50 , 40 to 80 μg/ml), tested at 24–72 h incubation, as shown for a multitude of cultured tumor cell lines such as mesothelioma (22–24), prostate (21,25), glioblastoma (19,20,26,27), ovarian (21,28), leukemia (28), colon (21,29–36), melanoma (21,37,38), osteosarcoma (40,41), pancreatic (41), lung (21), esophageal (42) and fibrosarcoma (41,43) as partly summarized by Jacobi et al (44). The effectiveness of Taurolidine in vitro was largely confirmed in vivo using various tumor cell lines as xenografts such as mesothelioma (23), prostate (25), ovarian (21,45), colon (29–31,34,35) and melanoma (37,46) as well as melanoma cells in a metastatic tumor model (46).…”

Section: Broad-spectrum Antineoplastic Activity Of Taurolidinementioning

confidence: 93%

Redox-directed cancer therapeutics: Taurolidine and Piperlongumine as broadly effective antineoplastic agents (Review)

Möhler

Pfirrmann

Frei

2014

International Journal of Oncology

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Targeting the oxygen stress response pathway is considered a promising strategy to exert antineoplastic activity in a broad spectrum of tumor types. Supporting this view, we summarize the mechanism of action of Taurolidine and Piperlongumine, two antineoplastic agents with strikingly broad tumor selectivity. Taurolidine enhances the oxidative stress (ROS) selectively in tumor cells. Its cytotoxicity for various tumor cells in vitro and in vivo, which includes tumor stem cells, is based on the induction of programmed cell death, largely via apoptosis but also necroptosis and autophagy. The redox-directed mechanism of action of Taurolidine is apparent from the finding that reducing agents e.g., N-acetylcysteine or glutathione impair its cytotoxicity, while its effectiveness is enhanced by agents which inhibit the cellular anti-oxidant capacity. A similar redox-directed antineoplastic action is shown by Piperlongumine, a recently described experimental drug of plant origin. Taurolidine is particularly advantageous in surgical oncology as this taurine-derivative can be applied perioperatively or systemically with good tolerability as shown in initial clinical applications.

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“…To date, few chemicals have been demonstrated to induce multiple types of programmed cell death. The concomitant occurrence of autophagy and necroptosis (34) or apoptosis and autophagic cell death has been reported (35). According to their data, two PCDs independently contribute to cell death execution or the one PCD is the consequence of the other PCD.…”

Section: Discussionmentioning

confidence: 99%

Etoposide induces a mixed type of programmed cell death and overcomes the resistance conferred by Bcl-2 in Hep3B hepatoma cells

Yoo

Yoon

Lee

et al. 2012

International Journal of Oncology

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Abstract. The Bcl-2 protein is known to exert not only antiapoptotic but also anti-autophagic activities. Numerous studies have demonstrated that etoposide, which is one of the most widely used cancer chemotherapy agents, induces apoptotic cell death. However, the exact molecular mechanism leading to cell death by etoposide remains to be resolved. This study aimed to dissect the mode of cell death induced by etoposide in Hep3B hepatoma cells. Furthermore, this study was conducted to examine whether etoposide overcomes the resistance conferred by Bcl-2 in Hep3B hepatoma cells. We observed that Hep3B cells treated with etoposide show not only apoptotic but autophagic phenotypes. Autophagy inhibition by 3-methyladenine (3MA) and caspase inhibition by zVAD-fmk effectively decreased autophagic and apoptotic phenotypes, respectively. However, either zVAD-fmk or 3MA only partially prevented cell death. These data indicate that etoposide concomitantly induces autophagic cell death and apoptosis in Hep3B cells. Importantly, etoposide can effectively induce cell death in Bcl-2-overexpressing Hep3B cells. Conversely, staurosporine, which exclusively induces apoptosis in Hep3B cells, did not efficiently induce cell death in Bcl-2-overexpressing Hep3B cells. Staurosporine-treated Hep3B cells also showed an autophagic phenotype. While autophagy is cell death-inducing in Hep3B cells treated with etoposide, it is cytoprotective in Hep3B cells treated with staurosporine. To this end, we observed that etoposide-induced mixed type of programmed cell death is associated with the dissociation of Bcl-2 from Beclin-1. Taken together, etoposide induces a mixed type of programmed cell death and overcomes the resistance conferred by Bcl-2 in Hep3B hepatoma cells.

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The antibacterial substance taurolidine exhibits anti-neoplastic action based on a mixed type of programmed cell death

Cited by 22 publications

References 39 publications

CD40 stimulation sensitizes CLL cells to rituximab-induced cell death

CD40 stimulation sensitizes CLL cells to rituximab-induced cell death

Redox-directed cancer therapeutics: Taurolidine and Piperlongumine as broadly effective antineoplastic agents (Review)

Etoposide induces a mixed type of programmed cell death and overcomes the resistance conferred by Bcl-2 in Hep3B hepatoma cells

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