An innovative therapeutic approach to man age melanoma may be represented by the introduction into clinical trials of naturally occurring compounds, whose antiproliferative and/or proapoptotic activity against malignant melanoma in both in vitro and in vivo models has been already demonstrated. add to favorites Among them, curcumin, a polyphenol extracted from the rhizome of the plant Curcuma longa, has been frequently reported to exert promising anticancer activity on several tumours. This molecule is highly pleiotropic, is able to enter cells, and interacts with numerous targets. Strong evidence demonstrated that curcumin inhibits prolifera Inhibitors,Modulators,Libraries tion, invasion, angiogenesis, and metastasis in several types of cancer through interaction with multiple cell sig nalling proteins.

Recently, curcumin has been shown to exert a good antiproliferative activity by inducing apoptosis in malignant melanoma. One of the most important pathway involved in the curcumin antitumour activity is the nuclear factor kB path way, particularly in melanoma cells. Indeed, curcumin is able to suppress the activation and Inhibitors,Modulators,Libraries phosphorylation of the inhibitor of NF kB alpha Inhibitors,Modulators,Libraries by inhibiting the IkB kinase and NF kB activity in human melanoma cell lines. Moreover, curcumin induces cell apoptosis and cell cycle arrest in G2/M phase in melanoma, through up regulation of p53, p21, p27 and checkpoint kinase 2. Recently, our group has synthesized a new curcumin related biphenyl structure whose antiproliferative and proapoptotic activities on melanoma cell lines were more effective, rapid and selective than those induced by curcumin.

The D6 compound was proved to promote apoptosis in melanoma cells through the mitochondrial intrinsic pathway. In vivo assays on mouse models confirmed the potential of D6 against mel anoma, showing a significant Inhibitors,Modulators,Libraries reduction of the tumour mass growth as compared to untreated control. To investigate the mechanisms of action of the D6 curcumin analogue against melanoma at the molecular level, we here studied its cellular uptake and its influence on cell cycle progression. Finally, a gene expression profile analysis of D6 treated melanoma cell lines was carried out on high density microarrays, in order to explore the mo lecular pathways activated after Inhibitors,Modulators,Libraries D6 enters cells. This gen omic technology is useful to dissect the molecular changes occurring inside cancer cells, and it is well documented for malignant melanoma.

In our study, the LB24Dagi primary melanoma cell line http://www.selleckchem.com/products/Paclitaxel(Taxol).html was selected for all the analyses, because it had been previously demonstrated to be the most sensitive line to D6 treatment among tested ones. Several molecular changes that can justify the antiproliferative and proapoptotic properties of D6 on mel anoma cells and likely contribute to its anti tumour effect have been here presented and discussed.