Magnetospirillum magneticum as a Living Iron Chelator Induces TfR1 Upregulation and Decreases Cell Viability in Cancer Cells

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.

Magnetospirillum magneticum triggers apoptotic pathways in human breast cancer cells

“…When the concentration of bacteria was increased even further (5000:1), the percentage of proliferating cancer cells dropped to almost to 0%, thus con rming that AMB-1 bacteria can cause cell cycle arrest in cancer cells. These ndings suggest that AMB-1 exert anti-proliferative effects, which are likely driven by the metabolic disturbance (possibly through iron chelation) [22] resulting in an inhibition of de novo DNA synthesis in MDA-MB-231 cells.…”

“…In this study, we attempted to recreate similar conditions as present in the tumor microenvironment in vitro and investigated the effect of Magnetospirillum magneticum, a unique strain of facultative anaerobic bacteria, on breast cancer cells MDA-MB-231. The magneto-aerotaxis properties of this strain are advantageous not only for reaching regions of oxygen concentration for optimal growth [39,40], but also because their elevated need for iron could be leveraged to deprive cancer cells of this vital nutrient [22]. We rst investigated what part of the original living and adherent cancer cell population could be identi ed after a 48 h hypoxic incubation with different ratios of AMB-1.…”

“…Hypoxia is an important mechanistic aspect involved in tumorigenesis and one of the characteristic features of the tumor microenvironment [31]. To closely mimic this property of solid tumors in our in vitro experiments, we used a chamber to replicate a low-oxygen environment [22] and thus enable to study the interplay between bacteria and cancer cells in conditions that would be normally present in tumors. First, we studied the behavior of breast cancer cells when exposed to live AMB-1 in an environment with a reduced presence of oxygen.…”

“…Additionally, these magnetosomes allow the MTB to be detected and guided by externally applied magnetic elds [20]. In bacterial cancer therapy, their native localization in hypoxic regions of solid tumors can be magnetically increased [15,21], and their enhanced requirement for iron might cause inducible iron competition and depletion within the tumor environment, possibly resulting in a decreased viability of cancer cells [22].…”

Tuning the Magnetic Response of Magnetospirillum magneticum by Changing the Culture Medium: A Straightforward Approach to Improve Their Hyperthermia Efficiency

“…In recent years, there has been growing interest in using not only the isolated magnetosomes but also the whole MTB as biomedical nanobio-robots, nanobiots , for different theranostic applications such as magnetic resonance imaging, magnetic particle imaging, drug delivery, magnetic hyperthermia, and so forth. ,,,− Seizing the advantage of the self-propulsion capability provided by their flagella and the presence of the magnetosome chain, these bacteria can be guided and manipulated by external magnetic fields toward specific areas inside the human body. On top of that, MTB, due to their preference for low oxygen concentration environments, are naturally attracted toward hypoxic areas, such as tumor regions .…”