Huazhong University of Science and Technology, Wuhan, Hubei, China.
Anticancer Res. 2011 Apr;31(4):1321-8.
BACKGROUND/AIM: Both the sulfated and non-sulfated derivatives (e.g. carboxymethyl benzylamide dextrans) of heparan sulfate were reported to have anticancer activity. On this basis, we introduced sulfates and phenyls in carboxymethyl benzylamide dextrans into chitosan, which is easily modified by different functional groups in any given position and then evaluated anticancer activity in breast cancer cells.
Chitosan derivatives were synthesized by introducing sulfate and phenyl groups into chitosan. Cell proliferation and apoptosis were assessed by (3)H-thymidine incorporation and fluorescence activated cell sorter analysis. Activation of Ras/MAPK signaling pathway downstream of fibroblast growth factor-2 (FGF-2) was analyzed by Western blot.
The sulfated chitosan (SCS) and the sulfated benzaldehyde chitosan (SBCS) significantly inhibited cell proliferation, induced apoptosis and blocked the FGF-2-induced phosphorylation of ERK in MCF-7 cells, SBCS had better inhibitory effects and a lower IC(50) compared to SCS.
The sulfated and benzaldehyde chitosans seem to be good potential compounds for anticancer drug design.
背景/目的：硫酸化和非硫酸化衍生物（如羧甲基苄基酰胺葡聚糖）的肝素硫酸盐据报道具有抗癌活性。在此基础上，我们将硫酸酯基和苯引入羧甲基苄基酰胺葡聚糖中的壳聚糖，壳聚糖很容易在任何给定位置被不同的官能团修饰，然后评估其在乳腺癌细胞中的抗癌活性。
通过将硫酸酯基和苯引入壳聚糖中合成壳聚糖衍生物。通过（3）H-胸苷掺入和荧光激活细胞分选分析评估细胞增殖和凋亡。通过 Western blot 分析碱性成纤维细胞生长因子-2（FGF-2）下游 Ras/MAPK 信号通路的激活情况。
硫酸化壳聚糖（SCS）和硫酸化苯甲醛壳聚糖（SBCS）显著抑制 MCF-7 细胞的增殖，诱导细胞凋亡，并阻断 FGF-2 诱导的 ERK 磷酸化，SBCS 的抑制效果优于 SCS，IC（50）值更低。
硫酸化和苯甲醛壳聚糖似乎是抗癌药物设计的潜在良好化合物。
