title: Akacid medical formulation induces apoptosis in myeloid and lymphatic leukemic cell lines in vitro and in vivo.
abstract: Akacid medical formulation (AMF) is an oligoguanidine that exerts biocidal activity against airborne and surface microorganisms including bacteria, viruses, fungi, and molds, while showing relatively low toxicity to humans. We have previously shown that AMF exerts antiproliferative effects on a variety of solid tumor cell lines. In this study we raised the question whether AMF could also substantially inhibit cell growth or induce apoptosis in cell lines derived from hematologic malignancies such as leukemia or lymphoma. We found that AMF has antiproliferative effects on various hematologic cell lines derived from human leukemia and lymphoma. Additionally, we show that AMF induces apoptosis in leukemia cell lines not only via the extrinsic and intrinsic pathway, but also in a caspase-independent manner. This effect was found also in G0-arrested cells. Finally, in our animal experiments utilizing male nu/nu Balb/c mice we found a significant growth retardation, which was immunohistochemically associated with a significantly lower number of KI67-positive cells and caspase-3 induction in AMF-treated mice.
authors: Department of Internal Medicine IV, Medical University of Innsbruck, Innsbruck, Austria.
authors: Hannes
authors: H
authors: Neuwirt
authors: Department of Internal Medicine IV, Medical University of Innsbruck, Innsbruck, Austria.
authors: Elisabeth
authors: E
authors: Wabnig
authors: Department of Internal Medicine V, Medical University of Innsbruck, Innsbruck, Austria.
authors: Clemens
authors: C
authors: Feistritzer
authors: Department of Experimental Urology, Medical University of Innsbruck, Innsbruck, Austria.
authors: Iris E
authors: IE
authors: Eder
authors: Department of Pediatrics, Medical University of Innsbruck, Innsbruck, Austria.
authors: Christina
authors: C
authors: Salvador
authors: Department of Experimental Urology, Medical University of Innsbruck, Innsbruck, Austria.
authors: Martin
authors: M
authors: Puhr
authors: Department of Experimental Urology, Medical University of Innsbruck, Innsbruck, Austria.
authors: Zoran
authors: Z
authors: Culig
authors: Department of Experimental Urology, Medical University of Innsbruck, Innsbruck, Austria.
authors: Petra
authors: P
authors: Massoner
authors: Department of Internal Medicine IV, Medical University of Innsbruck, Innsbruck, Austria.
authors: Martin
authors: M
authors: Tiefenthaler
authors: Department of Internal Medicine V, Medical University of Innsbruck, Innsbruck, Austria.
authors: Michael
authors: M
authors: Steurer
authors: Department of Internal Medicine I, Medical University of Innsbruck, Innsbruck, Austria.
authors: Guenther
authors: G
authors: Konwalinka
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D061945:Caspase Inhibitors / Q000494:pharmacology; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D004789:Enzyme Activation / Q000187:drug effects; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006146:Guanidines / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D007945:Leukemia, Lymphoid / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D007951:Leukemia, Myeloid / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D023041:Xenograft Model Antitumor Assays
chemical_list: C515423:Akacid-medical-formulation; D000970:Antineoplastic Agents; D061945:Caspase Inhibitors; D006146:Guanidines; D019253:Proto-Oncogene Proteins c-bcl-2; D020169:Caspases