A New Light-Sensor System Affecting Cancer Cell Fate

A new physiological photopolymerizing system with relevant effects on proteins and able to affect cancer cell fate was discovered here. The riboflavin–phosphocholine–light (RPL) system induces lysozyme (LYZ) photopolymerization in vitro, affecting the cell viability of cancer cells, in both 2-dimensional and 3-dimensional cell cultures. The RPL treatment of nontumoral, mesenchymal stem cells, or cancer cells shows a distinct behavior, depending on the ectopic presence of LYZ. Morphological changes and cellular aggregation of the cancer cells were induced by the treatment. The presence of both phosphocholine and high levels of LYZ expression at the breast cancer cell–cell interface seems to create a vulnerability for this new photodynamic system under visible light exposure. Further, we generated 2 new riboflavin–phosphocholine hydrogels (RPHy and RPHy-LYZ) by light-emitting diode exposure. A transdifferentiation into osteoblast-like cells of a triple-negative breast cancer cell line, embedded into RPHy, was detected, while cell death was observed using RPHy-LYZ. Our results reveal new properties of phosphocholine and LYZ with potential translational implications linked to the study of the transdifferentiation process of breast cancer cells and to therapeutical applications. The results highlight new aspects of the molecular mechanism by which riboflavin acts on cancer cells, paving the way for the use of the physiological expression levels of both phosphocholine and LYZ in selective therapies using the RPL system.