Role of the Copper(II) Complex Cu[15]pyN5 in Intracellular ROS and Breast Cancer Cell Motility and Invasion
Role of the Copper(II) Complex Cu[15]pyN5 in Intracellular ROS and Breast Cancer Cell Motility and Invasion
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DOI：
10.1111/cbdd.12521
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发表时间：
2015-10-01
影响因子：
3
通讯作者：
Oliveira, Nuno G.
中科院分区：
文献类型：
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作者：
Fernandes, Ana S.;Florido, Ana;Oliveira, Nuno G.
与转移相关的多种机制经历氧化还原调节。Cu[15]pyN（5）是一种具有氧化还原活性的铜（II）络合物，以前曾被研究为乳腺细胞中的化疗增敏剂。在两种人乳腺癌细胞系：MCF 7（低侵袭性）和MDA-MB-231（高侵袭性）中评估了Cu[15]pyN（5）和阿霉素（dox）的共同治疗效果。Cu[15]pyN（5）降低MCF 7-定向的细胞迁移。此外，用dox和Cu[15]pyN（5）共处理减少了MDA-MB-231细胞的蛋白水解侵袭。细胞脱离不受这些试剂的影响。Cu[15]pyN（5）和dox显著增加两种细胞系中的细胞内ROS。这种增加可能至少部分是由于H2 O2积累。Cu[15]pyN（5）与dox的组合可能对乳腺癌治疗有益，因为它可以帮助减少癌细胞的迁移和侵袭。此外，配体[15]pyN（5）对铜（II）具有高亲和力，并显示出潜在的抗血管生成特性。总的来说，我们提出了一种可能通过不同和互补机制阻止乳腺癌进展的潜在药物。
Multiple mechanisms related to metastases undergo redox regulation. Cu[15]pyN(5) is a redox-active copper(II) complex previously studied as a chemotherapy sensitizer in mammary cells. The effects of a cotreatment with Cu[15]pyN(5) and doxorubicin (dox) were evaluated in two human breast cancer cell lines: MCF7 (low aggressiveness) and MDA-MB-231 (highly aggressive). Cu[15]pyN(5) decreased MCF7-directed cell migration. In addition, a cotreatment with dox and Cu[15]pyN(5) reduced the proteolytic invasion of MDA-MB-231 cells. Cell detachment was not affected by exposure to these agents. Cu[15]pyN(5) and dox significantly increased intracellular ROS in both cell lines. This increase could be at least partially due to H2O2 accumulation. The combination of Cu[15]pyN(5) with dox may be beneficial in breast cancer treatment as it could help reduce cancer cell migration and invasion. Moreover, the ligand [15]pyN(5) has a high affinity for copper(II) and displays potential anti-angiogenic properties. Overall, we present a potential drug that might arrest the progression of breast cancer by different and complementary mechanisms.