Abstract：
Colorectal cancer (CRC) is one of the most common malignant tumours worldwide. Diarylheptanoids, secondary metabolites isolated from Zostera marina, are of interest in natural products research due to their biological activities. Zosterabisphenone B (ZBP B) has recently been shown to inhibit the viability of CRC cells. The aim of this study was to investigate the therapeutic potential of ZBP B for targeting human CRC cells. Cell viability was determined using the MTT assay. Flow cytometry and Western blot analyses were used to assess apoptosis and autophagy. A CRC xenograft model was used to evaluate the in vivo effect of ZBP B. No cytotoxic effect on HCEC cells was observed in the in vitro experiments. ZBP B caused morphological changes in HCT116 colon cancer cells due to an increase in early and late apoptotic cell populations. Mechanistically, ZBP B led to an increase in cleaved caspase-3, caspase-8, caspase-9, PARP and BID proteins and a decrease in Bcl-2 and c-Myc proteins. In the xenograft model of CRC, ZBP B led to a reduction in tumour growth. These results indicate that ZBP B exerts a selective cytotoxic effect on CRC cells by affecting apoptotic signalling pathways and reducing tumour growth in mice. Taken together, our results suggest that ZBP B could be a lead compound for the synthesis and development of CRC drugs.
摘要：
结直肠癌(CRC)是全球最常见的恶性肿瘤之一。二芳基庚类，从Zostera码头分离的次生代谢产物，由于其生物活性，对天然产物研究感兴趣。最近已显示ZoberabisphenoneB（ZBPB）抑制CRC细胞的活力。这项研究的目的是研究ZBPB靶向人类CRC细胞的治疗潜力。使用MTT测定法测定细胞活力。流式细胞术和蛋白质印迹分析用于评估细胞凋亡和自噬。使用CRC异种移植模型来评估ZBP的体内作用。在体外实验中未观察到对HCEC细胞的细胞毒性作用。ZBPB由于早期和晚期凋亡细胞群体的增加而引起HCT116结肠癌细胞的形态学变化。机械上,ZBPB导致裂解的caspase-3，caspase-8，caspase-9，PARP和BID蛋白增加，Bcl-2和c-Myc蛋白减少。在CRC的异种移植模型中，ZBPB导致肿瘤生长减少。这些结果表明ZBPB通过影响小鼠的凋亡信号传导途径和减少肿瘤生长而对CRC细胞发挥选择性细胞毒性作用。一起来看,我们的结果表明ZBPB可能是CRC药物合成和开发的先导化合物.
