Cytostatic and cytotoxic effects of cyclooxygenase inhibitors and their synergy with docosahexaenoic acid on the growth of human skin melanoma A-375 cells.

Recent studies have suggested the inhibition of cyclooxygenase-2 (COX-2) as strategy to prevent colorectal cancer. In this study, the cytostatic and cytotoxic effects of different non-steroidal anti-inflammatory drugs (NSAIDs), all of them are reported COX inhibitors, were investigated in human skin melanoma A-375 cells. Using BrdU-cell proliferation assay, we showed that 50 and 100 microM of celecoxib (CEL) reduced proliferation of the melanoma cells at 72-h incubations by 34.0% and 82.7%, respectively. As determined by Toxilight-cytotoxicity assay, the drug was only toxic to the cancer cells at 100 microM. Indomethacin (IND) also inhibited the cell proliferation by about 40% at 240 and 480 pM and was only slightly toxic to the melanoma. Neither aspirin (ASP) nor piroxicam (PIR) exhibited cytostatic or cytotoxic effect on the cancer cells. Combinatory effects of the above NSAIDs with dietary docosahexaenoic acid (DHA) on inhibiting growth of the melanoma cells were further elucidated. Each of the NSAIDs, at doses 10-480 pM, was incubated simultaneously with the melanoma cells and 160 pM of DHA for 72 h. Results from MTT assay showed that both CEL and IND, starting from 20 microM. exhibited additive effects on the DHA-induced growth inhibition. ASP also enhanced the DHA-induced growth inhibition by 42.8% at 480 microM. To our surprise, although PRX did not suppress the melanoma growth, the drug at 40-240 microM enhanced the DHA-induced growth inhibition by 15.9-66.4%, respectively. Results from these studies suggest that the anticancer effects of NSAIDs may not be explained solely by their COX-inhibitory activities. Further studies are therefore required to understand their modes of action, before they could be used alone or in combinations with other agents for cancer chemoprevention.

Antiviral property and mode of action of a sulphated polysaccharide from Sargassum patens against herpes simplex virus type 2.

A sulphated polysaccharide (SP2) was isolated from the brown alga Sargassum patens. SP2 inhibited the replication of herpes simplex virus type 2 (HSV-2) dose-dependently by 38.5-96.1% of the control level, after incubations with 0.78-12.5 microg/ml of the polysaccharide. SP2 exhibited extracellular virucidal activity only in high concentrations (>/=12.5 microg/ml) but significantly inhibited the virus attachment to its host cells by 45.1%, at concentration as low as 1 microg/ml. All the results from this study suggested that the antiviral mode of action of SP2 could be ascribed to the inhibition of virus adsorption, which is different from that of the current drug of choice acyclovir.

Evaluation of antioxidative activity of extracts from a brown seaweed, Sargassum siliquastrum.

Antioxidative activities of the extracts from Sargassum siliquastrum were determined using the inhibition of red blood cell (RBC) hemolysis induced by 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH) radicals, suppression of lipid peroxidation using rat brain homogenate, and scavenging activity of superoxide radicals. The dichloromethane fraction isolated from the methanol crude extract by differential solvent extractions exhibited the strongest antioxidant activity in both RBC hemolysis and lipid peroxidation assays. This fraction was further fractionated into four subfractions F1-F4 by silica gel column chromatography. F1 was found to be most effective in protecting RBC against AAPH radicals and in inhibiting lipid peroxidation. On the basis of thin-layer chromatography and UV and IR spectra analyses, all subfractions contained phenolic compounds. However, there was no correlation between the above antioxidant potency and total phenolic compounds estimated by using the Folin-Ciocalteau method.

Antiviral property and mechanisms of a sulphated polysaccharide from the brown alga Sargassum patens against Herpes simplex virus type 1.

A sulphated polysaccharide (SP-2a) from the brown alga Sargassum patens (Kütz.) Agardh (Sargassaceae) was found to significantly inhibit the in vitro replication of both the acyclovir (ACV)-sensitive and -resistant strains of Herpes simplex virus type 1 (HSV-1), in dose-dependent manners, with 50% inhibitions occurring with 1.5-5.3 microg/ml of the polysaccharide. SP-2a exhibited extracellular virucidal activity only against the ACV-sensitive strains, but not the resistant strain, at the concentration of 100 microg/ml. The strongest antiviral activities against the different strains of HSV-1 were observed when this polysaccharide was present during and after adsorption of the virus to host cells. The inhibitory effect of SP-2a on virus adsorption occurred dose-dependently in all the HSV-1 strains tested, and the adsorption of the ACV-resistant DM2.1 strain was reduced by 81.9% (relative to control) with 4 microg/ml of the polysaccharide. This study clearly demonstrated that the antiviral mode of action of SP-2a is mediated mainly by inhibiting virus attachment to host cells, and this sulphated polysaccharide might have different modes of action against the ACV-sensitive and -resistant strains of HSV-1.