Progression of human melanoma is prevented by NRF2 activation through NF-kB inhibition

Melanoma is the most invasive form of skin cancer characterized by a very low survival rate. Metastatic melanoma is often characterized by chemo-resistance, and the research of new possible adjuvant therapies to be associated with the conventional treatments are an important area of research. The oxidant/inflammatory cross-talk plays a key role in the signaling pathways involved in the progression of melanoma. A large body of evidence demonstrated a correlation between consumption of plant-based foods, and the reduced incidence of cancer. Besides their role in primary prevention, it is accepted that these compounds, mainly represented by phytochemicals, can prevent, or least decrease the metastasis process. Among different phytochemicals, Sulforaphane (SFN), a molecule derived from cruciferous vegetables, is one of the most studied in terms of human health benefit as it has been shown to be a strong activator of the transcription factor Nrf2, a master regulator of cellular defense machinery. In this scenario, in the present study we evaluated, in highly aggressive melanoma cell line SK-MEL 28, the ability of SFN in modulating the crosstalk between NRF2 and NF-kB (an inflammatory redox sensitive transcription factor) involved in the progression of metastatic melanoma. Our results showed that SFN, by activating NRF2 prevented the NF-kB inflammatory related responses, (i.e., decreased levels of COX2 and IL-6) in a HO-1 dependent mechanism. In addition, the ability of SFN to prevent metastatic melanoma progression via NRF2 and NF-kB modulation was also evaluated and confirmed in human melanoma spheroids. In conclusion our results bring new insights on the role of SFN as adjuvant compound in metastatic melanoma treatment by targeting the redox-inflammatory crosstalk involved in the progression of this very aggressive skin cancer.