A novel copper chelator for the suppression of colorectal cancer
A novel copper chelator for the suppression of colorectal cancer
复制标题
DOI：
10.1002/ddr.22034
复制
发表时间：
2023-01-19
影响因子：
3.8
通讯作者：
Liu，Yanrong
中科院分区：
文献类型：
--
作者：
Shi，Xiaolong;Li，Ying;Liu，Yanrong
铜离子在癌症的发展中起着至关重要的作用。肿瘤组织中富含铜离子，铜螯合剂可以潜在地螯合这些铜离子，从而发挥抗肿瘤作用。在这项研究中，我们报告了一种新型噻吩并[3，2-c]吡啶化合物的合成，我们称之为“JYFY-001”，由于包含了一个N-针对铜离子的（吡啶-2-基）乙酰胺部分。JYFY-001有效抑制癌症增殖，诱导细胞凋亡，降低大肠癌细胞外酸化率和耗氧率，JYFY-001还以剂量依赖方式抑制CRC移植瘤的生长，诱导肿瘤细胞凋亡，促进CRC移植瘤组织中淋巴细胞的浸润。JYFY-001还增强了程序性细胞死亡蛋白1（PD-1）抑制剂的抗肿瘤作用。通过对小鼠正常细胞活力和急性毒性试验的影响，证明了JYFY-001的相对良性性质。我们的研究结果表明，JYFY-001是一种很有前景的铜螯合剂，可用作靶向药物和免疫治疗的替代品用于CRC治疗。
Copper ions play a crucial role in the progression of cancers. Tumor tissue is rich in copper ions, and copper chelators could potentially scavenge these copper ions and thus exert an antitumor effect. In this study, we report the synthesis of a novel thieno[3,2‐c]pyridine compound we have called “JYFY‐001” that can act as the copper chelator thanks to the inclusion of anN‐(pyridin‐2‐yl)acetamide moiety that targets copper ions.JYFY‐001potently inhibited cancer proliferation, inducing cell apoptosis and impairing the extracellular acidification rate and oxygen consumption rate of colorectal cancer (CRC) cells.JYFY‐001also inhibited the growth of a CRC‐transplanted tumor in a dose‐dependent manner, inducing apoptosis of the tumor cells and promoting the infiltration of lymphocytes in the CRC‐transplanted tumor tissues.JYFY‐001also enhanced the antitumor effects of the programmed cell death protein 1 (PD‐1) inhibitor. The relatively benign nature ofJYFY‐001was demonstrated by the effect on normal cell viability and acute toxicity tests in mice. Our findings suggest thatJYFY‐001is a prospective copper chelator to be used as a targeted drug and a synergist of immunotherapy for CRC treatments.