Akacid Medical Formulation Induces Apoptosis in Myeloid and Lymphatic Leukemic Cell Lines In Vitro and In Vivo

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.阿卡西德医用制剂（Akacid medical formulation，AMF）是一种低聚胍类（oligiguanidine）化合物，可对空气传播及表面附着的微生物（包括细菌、病毒、真菌与霉菌）发挥杀生物活性，同时对人体毒性相对较低。此前我们已有研究证实，AMF对多种实体肿瘤细胞系具有抗增殖活性。本研究旨在探讨AMF是否同样能够显著抑制血液系统恶性肿瘤（hematologic malignancies）来源细胞系的细胞增殖，或诱导其发生细胞凋亡（apoptosis）——此类血液系统恶性肿瘤涵盖白血病与淋巴瘤。研究结果显示，AMF对多种人源白血病及淋巴瘤来源的血液系统细胞系均具有抗增殖活性。此外，本研究还证实，AMF诱导白血病细胞系凋亡的途径不仅包括外源性凋亡通路与内源性凋亡通路，还可通过半胱天冬酶非依赖（caspase-independent）的方式实现。该效应在G0期阻滞细胞（G0-arrested cells）中同样可被观测到。最后，在以雄性Balb/c nu/nu裸鼠开展的动物实验中，我们发现AMF给药组小鼠的肿瘤生长显著受阻；免疫组织化学分析显示，该组小鼠的Ki67阳性细胞数量显著减少，且半胱天冬酶-3（caspase-3）的表达被诱导上调。