Glinsky G V, Mossine V V, Price J E, Bielenberg D, Glinsky V V, Ananthaswamy H N, Feather M S
Cancer Research Center and Metastat, Inc., Columbia, MO, USA.
Clin Exp Metastasis. 1996 May;14(3):253-67. doi: 10.1007/BF00053899.
We studied the influence of 10 synthetic glycoamine analogs on colony formation in 0.3 and 0.9% agarose by metastatic human breast carcinoma (MDA-MB-435) and melanoma (TXM-13) cells. Nine synthetic analogs significantly inhibited the colony formation in 0.9% agarose of MDA-MB-435 human breast carcinoma cells; five compounds caused a 73-83% reduction of colony formation. Seven synthetic glycoamines caused a significant inhibition of colony formation in 0.9% agarose by TXM-13 melanoma cells with the inhibitory effect ranging from 71 to 87%. The 50% inhibition (I50) doses and relative activity rank of the compounds were similar for both breast carcinoma and melanoma cell lines. The murine B16 melanoma cell aggregation assay was employed to elucidate the potential mechanism(s) of the inhibitory activity of synthetic glycoamines. The relative activity ranks of the compounds based on the independently determined I50 doses for both cell aggregation and clonogenic growth assays were very similar for the four most active synthetic analogs and clearly indicated the importance of hydrophobic amino acid in mediating the bioactivity of synthetic glycoamines. In both experimental systems (clonogenic growth in agarose and cell aggregation assay) the leading compound was N-(1-deoxy-D-fructos-1-yl)-D-leucine (Fru-D-Leu) and the least active analog was N-(l-deoxy-D-fructos-1-yl)-glycine (Fru-Gly). These results show that synthetic glycoamines may act by competing for specific carbohydrate-lectin interactions, particularly those involving beta-galactoside-specific lectins expressed on metastatic cells.
我们研究了10种合成糖胺类似物对转移性人乳腺癌（MDA-MB-435）和黑色素瘤（TXM-13）细胞在0.3%和0.9%琼脂糖中集落形成的影响。9种合成类似物显著抑制了MDA-MB-435人乳腺癌细胞在0.9%琼脂糖中的集落形成；5种化合物使集落形成减少了73%-83%。7种合成糖胺显著抑制了TXM-13黑色素瘤细胞在0.9%琼脂糖中的集落形成，抑制效果在71%至87%之间。对于乳腺癌和黑色素瘤细胞系，这些化合物的50%抑制（I50）剂量和相对活性排名相似。采用小鼠B16黑色素瘤细胞聚集试验来阐明合成糖胺抑制活性的潜在机制。基于独立测定的I50剂量，对于细胞聚集和克隆生长试验，四种活性最高的合成类似物的化合物相对活性排名非常相似，清楚地表明了疏水氨基酸在介导合成糖胺生物活性中的重要性。在两个实验系统（琼脂糖中的克隆生长和细胞聚集试验）中，主要化合物是N-（1-脱氧-D-果糖-1-基）-D-亮氨酸（Fru-D-Leu），活性最低的类似物是N-（1-脱氧-D-果糖-1-基）-甘氨酸（Fru-Gly）。这些结果表明，合成糖胺可能通过竞争特定的碳水化合物-凝集素相互作用发挥作用，特别是那些涉及转移细胞上表达的β-半乳糖苷特异性凝集素的相互作用。
