Hayashi Keita, Walde Peter, Miyazaki Tatsuhiko, Sakayama Kenshi, Nakamura Atsushi, Kameda Kenji, Masuda Seizo, Umakoshi Hiroshi, Kato Keiichi
Division of Chemical Engineering, Graduate School of Engineering Science, Osaka University, 1-3 Machikaneyama-cho, Toyonaka 560-8531, Osaka, Japan.
J Drug Deliv. 2012;2012:842785. doi: 10.1155/2012/842785. Epub 2012 Dec 27.
Previously, we demonstrated that the novel lectin Eucheuma serra agglutinin from a marine red alga (ESA) induces apoptotic cell death in carcinoma. We now find that ESA induces apoptosis also in the case of sarcoma cells. First, propidium iodide assays with OST cells and LM8 cells showed a decrease in cell viability after addition of ESA. With 50 μg/ml ESA, the viabilities after 24 hours decreased to 54.7 ± 11.4% in the case of OST cells and to 41.7 ± 12.3% for LM8 cells. Second, using fluorescently labeled ESA and flow cytometric and fluorescence microscopic measurements, it could be shown that ESA does not bind to cells that were treated with glycosidases, indicating importance of the carbohydrate chains on the surface of the cells for efficient ESA-cell interactions. Third, Span 80 vesicles with surface-bound ESA as active targeting ligand were shown to display sarcoma cell binding activity, leading to apoptosis and complete OST cell death after 48 hours at 2 μg/ml ESA. The findings indicate that Span 80 vesicles with surface-bound ESA are a potentially useful drug delivery system not only for the treatment of carcinoma but also for the treatment of osteosarcoma.
此前，我们证明了一种来自海洋红藻的新型凝集素——麒麟菜凝集素（ESA）可诱导癌细胞发生凋亡性细胞死亡。我们现在发现，ESA在肉瘤细胞中也能诱导凋亡。首先，对OST细胞和LM8细胞进行碘化丙啶检测，结果显示添加ESA后细胞活力下降。使用50μg/ml的ESA时，24小时后OST细胞的活力降至54.7±11.4%，LM8细胞的活力降至41.7±12.3%。其次，使用荧光标记的ESA以及流式细胞术和荧光显微镜测量，结果表明ESA不与用糖苷酶处理过的细胞结合，这表明细胞表面的碳水化合物链对于有效的ESA-细胞相互作用很重要。第三，以表面结合ESA作为活性靶向配体的司盘80囊泡显示出肉瘤细胞结合活性，在2μg/ml ESA作用48小时后导致凋亡并使OST细胞完全死亡。这些发现表明，表面结合ESA的司盘80囊泡不仅是一种潜在的有用药物递送系统，可用于治疗癌症，也可用于治疗骨肉瘤。
