J Agric Food Chem. 2015 Jan 14;63(1):150-9. doi: 10.1021/jf503208p.
Nostoc commune has been traditionally used in China as a health food and medicine. The water stress proteins (WSP) of Nostoc commune are the major component of the extracellular matrix. This study purified and identified the water stress proteins (WSP1) from Nostoc commune Vauch., which could inhibit the proliferation of human colon cancer cell lines. The IC50 values of WSP1 against DLD1, HCT116, HT29, and SW480 cells were 0.19 ± 0.02, 0.21 ± 0.03, 0.39 ± 0.05, and 0.41 ± 0.01 μg/μL, respectively. Notably, it displayed very little effect on the normal human intestinal epithelial FHC cell line. The IC50 value of WSP1 against FHC cells was 0.67 ± 0.05 μg/μL. Moreover, the growth of DLD1 xenografted tumors in nude mice were significantly suppressed in the WSP1 treated group. Mechanistically, the cell-cycle analysis revealed that WSP1 induced growth inhibition by G1/S arrest. Meanwhile, Western blotting and immunohistochemistry assays showed WSP1 could activate caspase-8, -9, and -3, along with subsequent PARP cleavage. Furthermore, the pan-caspase inhibitor, z-VAD-FMK, partly reversed the effect caused by WSP1, confirming that WSP1 induced cell apoptosis through caspase-dependent pathway. Collectively, WSP1 has targeted inhibition for colon cancer proliferation both in vitro and in vivo and it is valuable for future exploitation and utilization as an antitumor agent.
普通念珠藻在中国传统上被用作保健食品和药品。普通念珠藻的水胁迫蛋白(WSP)是细胞外基质的主要成分。本研究从普通念珠藻 Vauch.中纯化并鉴定了水胁迫蛋白(WSP1),它可以抑制人结肠癌细胞系的增殖。WSP1 对 DLD1、HCT116、HT29 和 SW480 细胞的 IC50 值分别为 0.19 ± 0.02、0.21 ± 0.03、0.39 ± 0.05 和 0.41 ± 0.01 μg/μL。值得注意的是,它对正常的人肠道上皮 FHC 细胞系几乎没有影响。WSP1 对 FHC 细胞的 IC50 值为 0.67 ± 0.05 μg/μL。此外,WSP1 处理组荷瘤裸鼠的 DLD1 异种移植瘤的生长明显受到抑制。从机制上讲,细胞周期分析表明 WSP1 通过 G1/S 期阻滞诱导生长抑制。同时,Western blot 和免疫组化检测显示,WSP1 可以激活 caspase-8、-9 和 -3,并伴有随后的 PARP 切割。此外,泛 caspase 抑制剂 z-VAD-FMK 部分逆转了 WSP1 的作用,证实 WSP1 通过 caspase 依赖性途径诱导细胞凋亡。综上所述,WSP1 对结肠癌的增殖具有靶向抑制作用,无论是在体外还是在体内,都具有作为抗肿瘤药物的开发和利用价值。