Figure 2.

Potential effects and mechanisms of an exogenous siderophore treatment in cancer cells. (A) Under normal conditions, cancer cells increase their iron uptake, which increases the iron labile pool (Fe²⁺) and ROS generation, and has been related to increased invasion, proliferation and tumor growth. (B) During exogenous siderophore treatment, siderophores bind ferric iron (Fe³⁺) and decrease the levels of free iron available for bacteria, LCN2 and cancer cells. As a result, cancer cells display reduced proliferation and tumor growth, and induction of apoptosis. Proposed mechanisms include: reduction of ferric iron (Fe³⁺) availability, the intracellular iron pool (Fe²⁺), ROS generation and expression of the anti-apoptotic gene Bcl-2, increasing expression of p53 and the pro-apoptotic genes Bax and Fas, activating the pro-apoptotic pathway through DDIT3, and inhibiting HDAC.