Recent studies suggest that lysozyme, rich in hen egg, has an antitumor function. In the present study, we investigated the antitumor and antiangiogenesis effects of a newly isolated marine lysozyme both in vitro and in vivo. First, we showed that this marine-derived lysozyme specifically inhibits the proliferation of endothelial cells (ECV304) in a dose-dependent manner with no cytotoxicity (IC(50) = 3.64 microM). Second, we showed that this marine lysozyme directly suppresses neovascularization in chicken embryos using chorioallantoic membrane assay. Third, we demonstrated that this marine lysozyme markedly inhibits tumor growth in mice bearing either sarcoma 180 or hepatoma 22. Unexpectedly, hen egg lysozyme has no effects on the proliferation of endothelial cells in vitro or neovascularization in chicken embryos or tumor growth in nude mice at the same dosage range. Taken together, our studies clearly show that the newly identified marine lysozyme is a potent antitumor molecule, which may inhibit tumor growth and inhibit angiogenesis. We believe that this marine lysozyme may have a therapeutic value in antitumor drug development.

Aim: To investigate the mechanism of polypeptide from Chlamys farreri (PCF) protecting HaCaT cells from apoptosis induced by UVA plus UVB in vitro. Methods: An apoptotic model of UV irradiation-induced HaCaT cells was established. The 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay, agarose gel electrophoresis, biochemical methods, and Western blotting were employed in the study. Results: PCF inhibited the UV irradiation-induced apoptosis of HaCaT cells. PCF strongly reduced the intracellular reactive oxygen species level, enhanced activities of superoxide dismutase and glutathione peroxidase and increased the total anti-oxidative capacity in HaCaT cells following UV irradiation. Furthermore, we found that PCF could inhibit the phosphorylation of c-Jun amino-terminal kinase and the activity of caspase-3 in a concentrationdependent manner. Conclusion: PCF protected HaCaT cells from apoptosis induced by UVA plus UVB, mainly through decreasing the intracellular ROS level and increasing the activities of anti-oxidative enzymes to block the ROS-JNKcaspase-3-apoptosis signaling pathway.

Polypeptide from Chlamys farreri (PCF) is a novel marine active product isolated from gonochoric Chinese scallop Chlamys farreri which has recently been found to be an effective antioxidant. In this study, we assessed the effect of PCF on UVB-induced intracellular signalling of apoptosis in HaCaT cells. Pre-treatment with PCF significantly inhibited UVB-induced apoptosis in HaCaT cells. PCF strongly reduced the intracellular reactive oxygen species (ROS) level followed by inhibiting the release of cytochrome c. The expression of CD95 and Fas-associating protein with death domain (FADD) was eliminated in a dose-dependent manner by PCF pre-treatment in UVB-irradiated HaCaT cells, followed by inhibition of cleavage of procaspase-8, whose activation induced cell apoptosis. Furthermore, pre-treatment with the ROS scavenger N-acetylcysteine (NAC) and the caspase-8 inhibitor z-IETD-fmk was found to effectively prevent UVB-induced apoptosis, suggesting that UVB-induced HaCaT cell apoptosis was partially due to generation of ROS and activation of the caspase-8 pathway. Consequently, the protective effect of PCF against UVB irradiation in HaCaT cells is exerted by suppression of generation of ROS followed by inhibition of cytochrome c release and inactivation of Fas-FADD-caspase-8 pathway, resulting in blockage of UVB-induced apoptosis.

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