Ruthenium Polypyridyl Complexes That Induce Mitochondria-Mediated Apoptosis in Cancer Cells
Ruthenium Polypyridyl Complexes That Induce Mitochondria-Mediated Apoptosis in Cancer Cells
复制标题
诱导癌细胞线粒体介导的细胞凋亡的钌聚吡啶复合物
DOI：
10.1021/ic100277w
复制
发表时间：
2010-07-19
影响因子：
4.6
通讯作者：
Wong, Yum-Shing
中科院分区：
文献类型：
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作者：
Chen, Tianfeng;Liu, Yanan;Wong, Yum-Shing
基于顺铂的化疗的局限性，包括高毒性、不良副作用和耐药性，促使人们广泛研究替代的基于金属的癌症疗法。钌（Ru）具有适合于合理的抗癌药物设计和生物应用的一些有利性质。在本研究中，我们合成了一系列含有N，N-螯合配体的钌多吡啶配合物，检测了它们的抗癌活性，并阐明了它们导致癌细胞死亡的分子机制。结果表明，[Ru（phen）（2）-p-MOPIP]（PF 6）（2）center dot 2 H（2）O（RuPOP）是一种具有较强抗增殖活性的配合物，能够诱导人癌细胞凋亡，这种凋亡是由caspase介导的。在这些结果的基础上，我们建议RuPOP作为人类癌症，特别是黑色素瘤的化学预防和化学治疗剂可能是进一步评估的候选物。
The limitations of cisplatin-based chemotherapy, including high toxicity, undesirable side effects, and drug resistance, have motivated extensive investigations into alternative metal-based cancer therapies. Ruthenium (Ru) possesses several favorable properties suited to rational anticancer drug design and biological applications. In the present study, we synthesized a series of ruthenium polypyridyl complexes containing N,N-chelating ligands, examined their anticancer activities, and elucidated the molecular mechanisms through which they caused the cancer cell death. The results demonstrated that [Ru(phen)(2)-p-MOPIP](PF6)(2)center dot 2H(2)O (RuPOP), a complex with potent antiproliferative activity, is able to induce mitochondria-mediated and caspase-dependent apoptosis in human cancer cells. On the basis of these results, we suggest that RuPOP may be a candidate for further evaluation as a chemopreventive and chemotherapeutic agent for human cancers, especially for melanoma.