Blue light activates phase 2 response proteins and slows growth of A431 epidermoid carcinoma xenografts

Background: Recent studies suggest that light in the UVA range (320-400 nm) activates signaling pathways that are anti-inflammatory, antioxidative and play a critical role in protection against cancer. These effects have been attributed to NF-E2-related factor (NRF2)-mediated upregulation of 'phase 2' genes that neutralize oxidative stress and metabolize electrophiles. We had previously shown that small doses of blue light (400-500 nm) had selective toxicity for cultured oral tumor cells and increased levels of peroxiredoxin phase 2 proteins, which led to our hypothesis that blue light activates NRF2 signaling. Materials and Methods: A431 epidermoid carcinoma cells were treated in culture and as nude mouse xenografts with doses of blue light. Cell lysates and tumor samples were tested for NRF2 activation, and for markers of proliferation and oxidative stress. Results: Blue light activated the phase 2 response in cultured A431 cells and reduced their viability dose dependently. Light treatment of tumors reduced tumor growth, and levels of proliferating cell nuclear antigen (PCNA), and oxidized proteins. Discussion: Cellular responses to these light energies are worth further study and may provide therapeutic interventions for inflammation and cancer.