Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Carl Gustav Carus, Technische Universität Dresden, Fetscherstrasse 74, 01307 Dresden, Germany.
Department of Medicine III, University Hospital Carl Gustav Carus, Technische Universität Dresden, Fetscherstrasse 74, 01307 Dresden, Germany.
Mar Drugs. 2020 May 1;18(5):236. doi: 10.3390/md18050236.
Novel strategies to treat cancer effectively without adverse effects on the surrounding normal tissue are urgently needed. Marine sponges provide a natural and renewable source of promising anti-tumor agents. Here, we investigated the anti-tumor activity of Aerothionin and Homoaerothionin, two bromotyrosines isolated from the marine demosponge Aplysina cavernicola, on two mouse pheochromocytoma cells, MPC and MTT. To determine the therapeutic window of these metabolites, we furthermore explored their cytotoxicity on cells of the normal tissue. Both metabolites diminished the viability of the pheochromocytoma cell lines significantly from a concentration of 25 µM under normoxic and hypoxic conditions. Treatment of MPC cells leads moreover to a reduction in the number of proliferating cells. To confirm the anti-tumor activity of these bromotyrosines, 3D-pheochromocytoma cell spheroids were treated with 10 µM of either Aerothionin or Homoaerothionin, resulting in a significant reduction or even complete inhibition of the spheroid growth. Both metabolites reduced viability of normal endothelial cells to a comparable extent at higher micromolar concentration, while the viability of fibroblasts was increased. Our in vitro results show promise for the application of Aerothionin and Homoaerothionin as anti-tumor agents against pheochromocytomas and suggest acceptable toxicity on normal tissue cells.
急需找到新的策略，在不影响周围正常组织的情况下有效治疗癌症。海洋海绵为有前途的抗肿瘤药物提供了天然可再生的来源。在这里，我们研究了从海洋寻常海绵 Aplysina cavernicola 中分离出的两种溴代酪氨酸 Aerothionin 和 Homoaerothionin 对两种小鼠嗜铬细胞瘤细胞 MPC 和 MTT 的抗肿瘤活性。为了确定这些代谢物的治疗窗，我们还研究了它们对正常组织细胞的细胞毒性。在常氧和缺氧条件下，两种代谢物浓度为 25 µM 时，就显著降低了嗜铬细胞瘤细胞系的活力。MPC 细胞的处理还导致增殖细胞数量减少。为了证实这些溴代酪氨酸的抗肿瘤活性，用 10 µM 的 Aerothionin 或 Homoaerothionin 处理 3D 嗜铬细胞瘤细胞球体，导致球体生长显著减少甚至完全抑制。两种代谢物在较高的微摩尔浓度下对正常内皮细胞的活力降低到相当程度，而成纤维细胞的活力增加。我们的体外结果表明，Aerothionin 和 Homoaerothionin 有望作为抗嗜铬细胞瘤的抗肿瘤药物应用，并提示对正常组织细胞具有可接受的毒性。
