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



The 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.



Our 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.



These 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.
Division of Molecular and Clinical Research, St. Josef-Hospital, Ruhr-University Bochum, Bochum, Germany. marie.buchholz-a7y@rub.de.
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Buchholz
Division of Molecular and Clinical Research, St. Josef-Hospital, Ruhr-University Bochum, Bochum, Germany.
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Majchrzak-Stiller
Department of Molecular Gastrointestinal Oncology, Ruhr-University Bochum, Bochum, Germany.
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Hahn
Department of Molecular Gastrointestinal Oncology, Ruhr-University Bochum, Bochum, Germany.|Department of Internal Medicine, Knappschaftskrankenhaus, Ruhr-University Bochum, Bochum, Germany.
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Vangala
Geistlich Pharma AG, Wolhusen, Switzerland.
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Pfirrmann
Division of Molecular and Clinical Research, St. Josef-Hospital, Ruhr-University Bochum, Bochum, Germany.
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Uhl
Division of Molecular and Clinical Research, St. Josef-Hospital, Ruhr-University Bochum, Bochum, Germany.
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Braumann
Division of Molecular and Clinical Research, St. Josef-Hospital, Ruhr-University Bochum, Bochum, Germany.
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Chromik
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007274:Injections, Intraperitoneal; D051379:Mice; D015394:Molecular Structure; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013829:Thiadiazines / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D017382:Reactive Oxygen Species; D013829:Thiadiazines; C000625505:substance 2250 (tataurultam derivative); D020169:Caspases; C111424:taurultam
Apoptosis; Cancer; Chemotherapy; Substance 2250; Taurolidine