## 5 Studies and Mechanism about n-3 PUFAs and Melanoma
### Discrepancy in Results and Approaches to Studies in Humans
\begin{table}
\begin{tabular}{c c c c} \hline \hline
**Model** & **Dose** & **Results** & **Reference** \\ \hline In vitro & & - TNF-\(\alpha\) upregulates the expression of both COX-2 mRNA and PGE2 & \\ In vitro & & - PGE3 incubation significantly decreased invasive values & \\ (70 W human melanoma cell line that metastasizes to the brain in nude mice) & 50 uM each for 24 h of AA, & - DHA and EPA decreased COX-2 mRNA expression & [73] \\  & & EPA or DHA decreased the cell invasion, whereas AA caused & \\  & & EPA or DHA increased by 2.4 times & \\  & & - EPA and DHA downregulated both COX-2 mRNA and protein & \\  & & - expression, with a subsequent decrease in invasion. & \\ \hline In vitro & & - Significantly suppressed the anchorage independent & \\ (WM115 and WM266-4 & & - Inhibits melanoma cell growth, migration and invasion & \\ human melanoma, and & & - Inhibits the expression of several matrix metalloproteinases & \\ B16-F10 murine melanoma & & - These effects are related to the \(\beta\)-catenin increased nuclear & \\  & & expression and PKA-dependent phosphorylation, as well as to & \\  & & - increased expression of MITF. & \\ \hline In vitro & & - Decrease of proliferation, associated by oxidative protein and & \\ (A375, A2058, and G361 & & 100 mM) & - Increase of proliferation, associated by oxidative protein and & \\ human melanoma cells) & & - DNA damage was observed for EPA and DHA (50 mM and 100 mM) in A375, A2058, and G361 cells & \\  & & - In C32 (amendict melanoma), EPA and DHA inhibited cell & [59] \\ human melanoma cells) & & proliferation at 100 mM only and the effect & \\  & & - The C32 (amendict melanoma), EPA and DHA inhibited cell & [59] \\  & & - Both celecoxib and indomethacin, starting from 20 uM, & \\  & & exhibited additive effects on the DHA-induced growth inhibition. & \\  & & - Aspirin enhanced the DHA-induced growth inhibition by 42.8\% & \\  & & at 480 uM as well as prioxicum by 15.9–66.4\% at 40–240 uM. & \\ \hline In vitro & & - The constitutive expression and mRNA-expression of COX-2 & \\  & & protein was inhibited in a dose-dependent manner by & \\  & & 10–30 uM DHA & \\  & & - Degradation of COX-2 mRNA was accelerated by the presence & \\  & & of 30 uM DHA in cells whose mRNA transcription was & \\  & & inhibited by 10 g/mL actinomycin D. & \\  & & - DHA reduced the expression of cytosolic HuR (stabilizer of & \\  & & COX-2 mRNA) in a concentration- & \\ (Primary WM115 and WM266-4 metastatic melanoma cell line) & 10–30 uM DHA, EPA, oleic & time-dependent manner & \\  & & acid or linoleic acid for 72 h & - DHA and EPA inhibited the growth and apoptosis of both the & \\  & & cell lines and the effect was concentration dependent & \\  & & - DHA reduced the expression of total \(\beta\)-catenin in both the cell & lines studied \\  & & - DHA and EPA induce apoptosis in melanoma cells through & \\  & & caspase-3 pathway by increasing Bax proteins and decreasing & \\  & & Bcl-2 proteins, therefore, augmenting the Bax/Bcl-2 ratio. & \\  & & - The pro-apoptotic effect was observed for DHA and EPA and & \\  & & not observed with the other fatty acids oleic acid. & \\ \hline In vitro & & - Inhibits melanogenesis in cells through increasing & [187] \\ (B16-F10 mouse melanoma cells) & 3 days & tyrosinase degradation. & \\ \hline  & & - EPA suppresses membrane-associated Tyr and Tyrrp1 & \\  & & - PA induces formation of F-actin, while EPA decreases & \\  & & - Factine levels in melanoma cells & \\  & & - EPA and DHA suppressed gene expression of Glut-1 & \\  & & 50 uM of PA or EPA on & \\  & & - Pac increases and EPA decreases the level of Rab27a in & \\  & & culture for 24 h or 25 uM of & B16F10 cells & \\ G361, HOMO, and HTMMI & & DHA delayed the cell cycle of melanoma & \\  & & - DHA interacts with the receptor for activated C kinase 1, leading & \\  & & to the repression of melanoma cell proliferation through the & \\  & & inhibition of PKC signaling. & \\ \hline \hline \end{tabular}
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