Institute of Traditional Medicine, National Yang-Ming University, 155 Li-Nung St., Sec. 2, Shipai, Beitou, Taipei 112, Taiwan.
School of Pharmacy, College of Medicine, National Taiwan University, 33 Linsen S. Rd., Zhongzheng, Taipei, Taiwan.
Carbohydr Polym. 2019 Jul 15;216:204-212. doi: 10.1016/j.carbpol.2019.04.017. Epub 2019 Apr 5.
Sulfated polysaccharides (SPSs) are polysaccharides (PSs) with high sulfate functionalization and possess bioactivities. This study aimed to increase the sulfate content of SPSs in Antrodia cinnamomea through sulfate feeding. Feeding A. cinnamomea with sodium thiosulfate was found to increase yields of PSs and SPSs in A. cinnamomea. The SPSs thus obtained (ST-SPS) were further isolated, showing enhanced sulfate content of 2.5 mmol/g. Sodium thiosulfate induced changes in molecular weight from 320 kDa to 1342 kDa, and area percentage of low-molecular-weight ST-SPS (< 20 kDa) was decreased. Functional studies revealed that sodium thiosulfate increased the ST-SPS anticancer efficacy in cancer cells via inhibition of EGFR/AKT signaling. Moreover, the ST-SPS enhanced synergistically cisplatin-, gefitinib- and 5 FU-induced cytotoxic effects in lung cancer H1975 cells and colon cancer CT26 cells. This study is the first to demonstrate that sodium thiosulfate induced changes in properties of A. cinnamomea with the anticancer mechanisms of ST-SPS.
硫酸化多糖(SPSs)是硫酸化程度较高的多糖,具有生物活性。本研究旨在通过硫酸根供体来提高桑黄中 SPS 的硫酸化程度。向桑黄投喂硫代硫酸钠可提高桑黄中 PS 和 SPS 的产量。由此得到的 SPS(ST-SPS)进一步分离,硫酸化程度提高至 2.5mmol/g。硫代硫酸钠诱导分子量从 320kDa 变化至 1342kDa,且低分子量 ST-SPS(<20kDa)的面积百分比降低。功能研究表明,通过抑制 EGFR/AKT 信号通路,硫代硫酸钠增加了 ST-SPS 在癌细胞中的抗癌功效。此外,ST-SPS 增强了顺铂、吉非替尼和 5-FU 在肺癌 H1975 细胞和结肠癌 CT26 细胞中的协同细胞毒性作用。本研究首次证明,硫代硫酸钠诱导了桑黄特性的变化,其 SPS 的抗癌机制也得到了证实。