Low-Power Blue LED Modulates NF-κB and Proinflammatory Cytokines in Doxorubicin-Treated MDA-MB-231 Cells

Abstract

Doxorubicin is a crucial chemotherapy used in the treatment of triple-negative breast cancer (TNBC) patients, but elevated doxorubicin doses may induce therapeutic resistance. To overcome this limitation, we have previously established a photodynamic therapeutic (PDT)-like strategy that irradiates doxorubicin-treated cells with a low-power nonionizing blue LED device. This combined treatment increases the production of reactive oxygen species to promote cell death, consequently enabling reduced doxorubicin dosages. Yet, precisely determining the molecular mechanisms that drive this outcome is still required for advancing such PDT-like approach. Here, we aimed to correlate the expression of the inflammatory markers NF-κB, IL-8, IL-6, and IL-1β with the survival of TNBC cells submitted to our PDT-like protocol. Our results show that NF-κB/p65 nuclear levels were enhanced in MDA-MB-231 cells treated with doxorubicin and blue LED. Moreover, this PDT-like strategy increased IL-6 mRNA levels in MDA-MB-231 cells. IL-1β and IL-8 mRNA were upregulated in samples incubated with doxorubicin regardless of concomitant irradiation with blue LED. These results show that our PDT-like protocol is effective in elevating inflammatory signals, shedding light on the molecular mechanisms that underlie the efficacy of this innovative anticancer therapeutic approach.