期刊
REDOX BIOLOGY
卷 20, 期 -, 页码 367-378出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.redox.2018.10.016
关键词
Cancer; Cell migration; Cell invasion; SOD mimics; Manganese porphyrins; Redox modulation
资金
- Fundacao para a Ciencia e a Tecnologia (FCT, Portugal) [UID/DTP/04567/2016, UID/DTP/04138/2013]
- Associacao Lusofona para o Desenvolvimento da Investigacao e Ensino em Ciencias da Satide -Cooperativa de Formacao e Animacao Cultural crl (ALIES-COFAC, Portugal)
- European Cooperation in Science and Technology (COST, European Union) [BM1203 EU-ROS]
Manganese(III) porphyrins (MnPs) are superoxide dismutase (SOD) mimics with demonstrated beneficial effects in cancer treatment in combination with chemo- and radiotherapy regimens. Despite the ongoing clinical trials, little is known about the effect of MnPs on metastasis, being therefore essential to understand how MnPs affect this process. In the present work, the impact of the MnP MnTnHex-2-PyP5 in metastasis-related processes was assessed in breast cancer cells (MCF-7 and MDA-MB-231), alone or in combination with doxorubicin (dox). The co-treatment of cells with non-cytotoxic concentrations of MnP and dox altered intracellular ROS, increasing H2O2. While MnP alone did not modify cell migration, the co-exposure led to a reduction in collective cell migration and chemotaxis. In addition, the MnP reduced the dox-induced increase in random migration of MDAMB-231 cells. Treatment with either MnP or dox decreased the proteolytic invasion of MDA-MB-231 cells, although the effect was more pronounced upon co-exposure with both compounds. Moreover, to explore the cellular mechanisms underlying the observed effects, cell adhesion, spreading, focal adhesions, and NF-KB activation were also studied. Although differential effects were observed according to the endpoints analysed, overall, the alterations induced by MnP in dox-treated cells were consistent with a therapeutically favorable outcome.
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