Abstract LB_B23: Magnetospirillum magneticum promotes iron competition and triggers apoptosis in human cancer cells

Abstract

Abstract Bacteria are increasingly envisioned as living agents that can be administered to patients to carry out therapeutic actions. Interest has been growing over the past years in harnessing these microorganisms for cancer treatment as dynamic vectors with enhanced tumor-targeting properties. While bacterial traits, such as modulation of an immune response, local secretion of toxins, and proliferation in tumors have been well studied, less is known about bacteria as competitors for nutrients. We, therefore, investigated the use of magnetotactic bacteria as living iron chelators in the tumor microenvironment by studying the resulting competition for this vital nutrient, and by investigating the consequent metabolic effects in cancer cells. To do this, we first recreated a hypoxic environment by establishing an in vitro co-culture system consisting of the magnetotactic strain Magnetospirillum magneticum AMB-1 incubated under low-oxygen conditions with human cancer cells. We first quantified bacterial siderophore production and found it to be equivalent to a relevant concentration of deferoxamine (DFO), a potent drug used in iron chelation therapy. Further experiments then revealed an increased expression of transferrin receptor 1 (TfR1) on the cell surface and a significant decrease of viability in various cancer cell lines, indicating the bacteria’s ability to alter iron homeostasis. Metabolic effects exerted by AMB-1 were then further investigated. We demonstrated a lower rate of cellular proliferation correlating with a growing ratio of bacteria to cancer cells. Additional experiments also confirmed elevated apoptotic states and an enhanced activity level of executioner caspases in cancer cells, with an increasing number of AMB-1 in the culture. Lastly, the performed assays uncovered several apoptosis-related proteins that displayed altered levels when AMB-1 bacteria were added to the culture. Overall, our findings show the potential of magnetotactic bacteria to act as self-replicating iron-chelating agents that interfere with the iron homeostasis of cancer cells and decrease cancer cell viability. The presented data suggests involvement of triggered apoptotic signals that correlate with an increasing number of AMB-1 in the culture. This intrinsic capability of AMB-1 to induce apoptosis in breast cancer cells thus represents an encouraging strategy that could serve as an additional antineoplastic approach to reinforce current bacterial cancer therapies. Citation Format: Stefano Menghini, Matej Vizovišek, Ping Shu Ho, Jonathas Enders, Simone Schürle. Magnetospirillum magneticum promotes iron competition and triggers apoptosis in human cancer cells [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr LB_B23.