In
malignant melanoma complex reprogramming of cell death and survival pathways leads to increased chemoresistance and poor longer-term survival.
Sulforaphane (SF) is a promising
isothiocyanate compound occurring in cruciferous plants with reported antiproliferative and proapoptotic activity in several tumor cell lines including
melanoma. In this work we investigated the effects of SF in several
melanoma cell lines and fresh
melanoma cultivates. We found that SF is cytotoxic and induces mitochondrial, caspase-dependent apoptosis in our study model, however with lower efficiency in fresh
melanoma cultivates. Moreover, our results indicate that in
melanoma cell lines and fresh
melanoma cultivates SF induces multiple signaling including oxidative stress-mediated activation of DNA-damage response pathway, changes in p38
kinase activity and enhanced expression of Bax and Puma proapoptotic
proteins. In addition, in SF-exposed p53-mutant
melanoma cells Puma expression seem to be under p38 control and acts as a compensatory proapoptotic mechanism. Conversely, decreased apoptosis in SF-exposed
melanoma cultivates might be attributed to Akt-mediated suppression of p38 as well as p53 activity. Together, our results suggest that SF inhibits growth and proliferation and induces mitochondrial apoptosis both in
melanoma cell lines as well as in fresh
melanoma cultivates. This proapoptotic effect might be enhanced in combination with Akt inhibitors, in particular in
melanoma samples. SF is thus commendable for further preclinical testing, both as a single agent as well as in combination regimens.