The manganese(III) porphyrin MnTnHex-2-PyP ⁵⁺ modulates intracellular ROS and breast cancer cell migration: Impact on doxorubicin-treated cells

Abstract

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-PyP ⁵⁺ 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 H ₂O ₂. 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 MDA-MB-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-κB 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.

Graphical abstract

Highlights

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  MnPs are SOD mimics with potential therapeutic applications in cancer.

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  The impact of an MnP on breast cancer metastasis-related processes was assessed.

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  Treatment with MnP+dox decreased collective cell migration, chemotaxis and invasion.

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  MnP also reduced the dox-induced increase in random migration of MDA-MB-231 cells.

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  Combination of MnP with dox revealed therapeutically favorable effects.