Cyclooxygenase-2 (COX-2) is important in the progression of epithelial tumors. Evidence indicates that -6 PUFAs such as arachidonic acid (AA) promote the growth of tumor cells; however, -3 fatty acids [eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] inhibit tumor cell proliferation. We investigated the effects of -3 PUFA on the expression and function of COX-2 in 70W, a human melanoma cell line that metastasizes to the brain in nude mice. We show that 1 ) tumor necrosis factor-␣ upregulates the expression of both COX-2 mRNA and prostaglandin E 2 (PGE 2 ) production, and 2 ) -3 and -6 PUFA regulate COX-2 mRNA expression and PGE 2 production. AA increased COX-2 mRNA expression and prostaglandin production in -6-stimulated 70W cells. Conversely, COX-2 mRNA expression decreased in cells incubated with EPA or DHA. AA increased Matrigel™ invasion 2.4-fold, whereas EPA or DHA did not. Additionally, PGE 2 increased in vitro invasion 2.5-fold, whereas exposure to PGE 3 significantly decreased invasion. Our results demonstrate that incubation of 70W cells with either AA or PGE 2 increased invasiveness, whereas incubation with EPA or DHA downregulated both COX-2 mRNA and protein expression, with a subsequent decrease in Matrigel™ invasion. Taken together, these results indicate that -3 PUFA regulate COX-2-mediated invasion in brain-metastatic melanoma.

The soft coral Sarcophyton glaucum is a rich resource of several bioactive cembranoids. Sarcophytol A (1) and sarcophine (2) are cembranoid diterpenes reported from this soft coral and extensively investigated for their cancer chemopreventive properties. This study aimed at investigating the antimetastatic potential of the major cembranoids, sarcophine (2) and 2-epi-16-deoxysarcophine (3), from the Red Sea soft coral S. glaucum. Biocatalytic transformation of 3 using Rhizopus stolonifer ATCC 6227a and Absidia spinosa ATCC 6648 afforded four new metabolites, 5-7 and 9, along with the known 9alpha-hydroxysarcophine (8). Sarcophine, 2-epi-16-deoxysarcophine, and metabolites 5-9 revealed significant antimetastatic activity against the highly metastatic mouse melanoma cell line (B16B15b). Cembranoids demonstrate a great potential for further development as antimetastatic agents.