Abstract
Interest has grown in harnessing biological agents for cancer treatment as dynamic vectors with enhanced tumor targeting. While bacterial traits such as proliferation in tumors, modulation of an immune response, and local secretion of toxins have been well studied, less is known about bacteria as competitors for nutrients. Here, we investigated the use of a bacterial strain as a living iron chelator, competing for this nutrient vital to tumor growth and progression. We established an in vitro co-culture system consisting of the magnetotactic strain Magnetospirillum magneticum AMB-1 incubated under hypoxic conditions with human melanoma cells. Siderophore production by 108 AMB-1/mL in human transferrin (Tf)-supplemented media was quantified and found to be equivalent to a concentration of 3.78 µM ± 0.117 µM deferoxamine (DFO), a potent drug used in iron chelation therapy. Our experiments revealed an increased expression of transferrin receptor 1 (TfR1) and a significant decrease of cancer cell viability, indicating the bacteria’s ability to alter iron homeostasis in human melanoma cells. Our results show the potential of a bacterial strain acting as a self-replicating iron-chelating agent, which could serve as an additional mechanism reinforcing current bacterial cancer therapies.
Highlights
Due to limited selectivity in systemically delivered cancer therapeutics, interest has grown in harnessing bacteria as living, tumor-targeting anticancer agents
We showed that magnetotactic bacteria AMB-1 impact cancer cell viability, suggesting that they affect cancer cell growth in vitro
AMB-1 are a strain of magnetotactic bacteria known to preferably grow at temperatures around 25–30 ◦C [39,40]
Summary
Due to limited selectivity in systemically delivered cancer therapeutics, interest has grown in harnessing bacteria as living, tumor-targeting anticancer agents. The therapeutic potential of facultative anaerobic bacteria has been supported by studies demonstrating the delivery of non-pathogenic strains of Escherichia coli to solid flank tumors with associated tumor regression [1]. Colonizing bacteria can engage in nutrient competition within the tumor microenvironment [8,9,10]. While the starvation of glucose as a crucial energy source to all cells has been studied extensively [11,12,13], other nutrients that are in high demand by cancer cells might serve as more specific, vulnerable targets for deprivation
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