Induction of tumor cell apoptosis by taurine Schiff base copper complex is associated with the inhibition of proteasomal activity.
Induction of tumor cell apoptosis by taurine Schiff base copper complex is associated with the inhibition of proteasomal activity.
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DOI：
10.3892/ijmm_00000072
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发表时间：
2008
影响因子：
5.4
通讯作者：
Xia Zhang;C. Bi;Yu-hua Fan;Q. Cui;Di Chen;Yan Xiao;Q. Dou
中科院分区：
文献类型：
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作者：
Xia Zhang;C. Bi;Yu-hua Fan;Q. Cui;Di Chen;Yan Xiao;Q. Dou
席夫碱因其抗菌和抗肿瘤特性已被深入研究。铜是肿瘤血管生成过程中必不可少的辅助因子，而其他过渡金属则不是。一直以来，在包括乳腺癌、前列腺癌、结肠癌、肺癌和脑癌在内的许多人类癌症中都发现血清或组织中铜含量较高，这支持了铜可作为癌症治疗的一种新的选择性靶点的观点。在当前的研究中，我们假设一种合成的牛磺酸席夫碱铜配合物（化合物1）可通过直接抑制蛋白酶体活性来抑制肿瘤细胞生长。化合物1能有效抑制人乳腺癌MDA - MB - 231细胞和白血病Jurkat T细胞中纯化的20S和26S蛋白酶体的活性。化合物1对肿瘤细胞蛋白酶体活性的抑制导致泛素化蛋白以及蛋白酶体靶蛋白p27和Bax的积累，进而诱导细胞凋亡。我们的研究结果有力地表明，牛磺酸席夫碱铜配合物作为有效的蛋白酶体抑制剂，极有可能被开发成为新型抗癌药物。
Schiff bases have been intensively investigated due to their antibacterial and antitumor properties. Copper is a cofactor essential for the tumor angiogenesis processes, whereas other transition metals are not. Consistently, high serum or tissue levels of copper were found in many types of human cancer including breast, prostate, colon, lung, and brain, supporting the idea that copper could be used as a novel selective target for cancer therapies. In the current study we hypothesize that a synthetic taurine Schiff base copper complex (Compound 1) could suppress tumor cell growth via the direct inhibition of proteasomal activity. Compound 1 potently inhibits the activity of purified 20S and 26S proteasome in human breast cancer MDA-MB-231 and leukemia Jurkat T cells. Inhibition of tumor cellular proteasomal activity by Compound 1 results in the accumulation of ubiquitinated protein and the proteasome target proteins p27 and Bax, followed by the induction of apoptosis. Our results strongly suggest that taurine Schiff base copper complexes, as potent proteasome inhibitors, have great potential to be developed into novel anticancer drugs.