Antiproliferative activity of eugenol and curcumin related biphenyls on malignant melanoma cell lines

Malignant melanoma (MM) is one of the most aggressive cancer and chemotherapeutic agents currently in use are still unsatisfactory. Prevention and early diagnosis are the only tools against this cancer whose incidence and mortality rates have been highly increased during the last decades in western countries. On the way of developing new therapeutic drugs against cancer, we aimed to characterize different compounds of natural origin with cytotoxic and/or antiproliferative activity in MM. Eugenol and curcumin are main components of several spices such as clove oil and turmeric spice, respectively, and both have been described as antiossidant, anti-inflammatory and antitumoral agents. We have tested several eugenol related biphenyls for their antiproliferative activity against MM cell lines showing that the enantiomeric form (aS) of the dibromo-deidrodieugenol (S7-S)was the most active with IC50 ranging around 20-30 ?M and without affecting cultured human fibroblasts (M.Pisano et al., 2007). Pro-apoptotic activity? Curcumin itself has been shown to suppress cellular transformation, proliferation, invasion and angiogenesis and we confirmed its potent antiproliferative activity in our MM cell lines (IC50 <= 10?M). Starting from curcumin several biphenyl compounds were synthesized and five of them (D2-D5) were tested on MM cells in order to evaluate their potential antiproliferative activity in comparison with curcumin itself and with the eugenol-related biphenyls. From these preliminary experiments we are able to say that curcumin and its related biphenyls are much more active in inhibiting proliferation of MM cells comparing with the S7-S activity. Among the five curcumin related biphenyls one of them (D6) shows antiproliferative activity at concentrations even lower (IC50 around 1- 2 ?M ) than curcumin. Cultured human fibroblasts treated with D6 at these concentrations do not seem to be affected in their proliferation rate. Wash out experiments and cell viability assays are on going to better define the antiproliferative activity and the mechanism of action of this compound.