Laboratory for Molecular Neuro-Oncology, Hertie Institute for Clinical Brain Research and Center Neurology, University of Tübingen, Otfried-Müller-Straße 27, 72076 Tübingen, Germany.
Evid Based Complement Alternat Med. 2012;2012:501796. doi: 10.1155/2012/501796. Epub 2012 Oct 22.
In Europe, commercially available extracts from the white-berry mistletoe (Viscum album L.) are widely used as a complementary cancer therapy. Mistletoe lectins have been identified as main active components and exhibit cytotoxic effects as well as immunomodulatory activity. Since it is still not elucidated in detail how mistle toe extracts such as ISCADOR communicate their effects, we analyzed the mechanisms that might be responsible for their antitumoral function on a molecular and functional level. ISCADOR-treated glioblastoma (GBM) cells down-regulate central genes involved in glioblastoma progression and malignancy such as the cytokine TGF-β and matrix-metalloproteinases. Using in vitro glioblastoma/immune cell co-cultivation assays as well as measurement of cell migration and invasion, we could demonstrate that in glioblastoma cells, lectin-rich ISCADOR M and ISCADOR Q significantly enforce NK-cell-mediated GBM cell lysis. Beside its immune stimulatory effect, ISCADOR reduces the migratory and invasive potential of glioblastoma cells. In a syngeneic as well as in a xenograft glioblastoma mouse model, both pretreatment of tumor cells and intratumoral therapy of subcutaneously growing glioblastoma cells with ISCADOR Q showed delayed tumor growth. In conclusion, ISCADOR Q, showing multiple positive effects in the treatment of glioblastoma, may be a candidate for concomitant treatment of this cancer.
在欧洲，市售的白浆果槲寄生（Viscum album L.）提取物被广泛用作癌症的辅助治疗方法。已鉴定出槲寄生凝集素为主要活性成分，具有细胞毒性作用和免疫调节活性。由于尚未详细阐明像 ISCADOR 这样的槲寄生提取物如何传递其作用，我们在分子和功能水平上分析了可能负责其抗肿瘤功能的机制。ISCADOR 处理的脑胶质瘤（GBM）细胞下调与 GBM 进展和恶性相关的中央基因，如细胞因子 TGF-β和基质金属蛋白酶。通过体外脑胶质瘤/免疫细胞共培养试验以及细胞迁移和侵袭测量，我们可以证明在脑胶质瘤细胞中，富含凝集素的 ISCADOR M 和 ISCADOR Q 可显著增强 NK 细胞介导的 GBM 细胞裂解。除了免疫刺激作用外，ISCADOR 还降低了脑胶质瘤细胞的迁移和侵袭潜力。在同种和异种脑胶质瘤小鼠模型中，ISCADOR Q 预处理肿瘤细胞和对皮下生长的脑胶质瘤细胞进行瘤内治疗均显示出肿瘤生长的延迟。总之，ISCADOR Q 在治疗脑胶质瘤方面具有多种积极作用，可能是该癌症联合治疗的候选药物。
