Syntheses and anti-cancer activity of CO-releasing molecules with targeting galactose receptors
Syntheses and anti-cancer activity of CO-releasing molecules with targeting galactose receptors
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DOI：
10.1039/c8ob01921e
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发表时间：
2018-11-21
影响因子：
3.2
通讯作者：
Liu, Bin
中科院分区：
文献类型：
--
作者：
Li, Jili;Zhang, Jinlong;Liu, Bin
含钴的CO释放分子（CORM）具有多种生物活性，但大多不溶于水，对组织器官没有选择性。基于受体对半乳糖或唾液酸的特异性识别，合成并评估了一系列基于碳水化合物的CORM。测试结果表明所有配合物均表现出抗癌活性。其中，半乳糖（1）、GalNAc（8）和唾液酸（10）复合物的作用非常明显。复合物1对HeLa、HePG2、MCF-7和HT-29细胞增殖的活性高于顺铂(DDP)，与正常细胞W138相比，其选择性远优于DDP。此外，还研究了 HePG2、HT-29、A549 和 RAW264.7 细胞系对复合物 1、8 和 10 的摄取。各细胞系对复合物1的摄取比例不同，四种细胞系中摄取比例的顺序为HePG2>HT-29>RAW264.7>A549。孵育8小时后，HePG2细胞吸收了超过60%的复合物1，而A549仅吸收了27.8%。对于复合物8，摄取趋势与复合物1相似，被四种癌细胞全部吸收，但摄取率较低。然而不同的是，复合物 10 被巨噬细胞 RAW264.7 大量吸收，其次是 HePG2；孵育8小时后，RAW264.7的摄取率超过50%。此外，还探讨了作用机制，结果表明复合物抑制细胞周期阻滞在G2/M期；复合物1上调caspase-3和Bax的表达水平，下调Bcl-2的表达，引起HePG2细胞凋亡。
CO-releasing molecules (CORMs) containing cobalt have many bioactivities, but most of them do not dissolve in water and have no selectivity to tissue and organs. On the basis of the specific recognition of galactose or sialic acid by a receptor, a series of CORMs based on carbohydrates were synthesized and evaluated. The test results show that all the complexes displayed anticancer activity. Among them, the effects of the complexes of galactose (1), GalNAc (8) and sialic acid (10) were very distinct. Complex 1 displayed higher activity against HeLa, HePG2, MCF-7 and HT-29 cell proliferation than cis-platin (DDP), and its selectivity was far much better than DDP compared with normal cell W138. Furthermore, the uptakes of complexes 1, 8 and 10 by HePG2, HT-29, A549 and RAW264.7 cell lines were studied. The uptake ratio of each cell line for complex 1 was different, and the order of uptake ratio in the four cell lines was HePG2 > HT-29 > RAW264.7 > A549. The HePG2 cells absorbed complex 1 beyond 60% after incubation for 8 h, while A549 absorbed only 27.8%. For complex 8, the uptake trend was similar to that of complex 1 with it being absorbed by all the four cancer cells, but the uptake rate was lower. However, differently, complex 10 was absorbed heavily by macrophage RAW264.7, followed by HePG2; after 8 h incubation, the uptake ratio of RAW264.7 was over 50%. In addition, the mechanism of action was explored, and the results showed that the complexes inhibited cell cycle arrest at the G2/M phase; complex 1 up-regulated the expression levels of caspase-3 and Bax, and down-regulated the Bcl-2 expression, giving rise to HePG2 cell apoptosis.