Summary COX-2 and its product PGE2 enhance carcinogenesis and tumor progression, which has been previously reported in melanoma. As most COX inhibitors cause much toxicity, the downstream microsomal PGE2 synthase-1 (mPGES1) is a consideration for targeting. Human melanoma TMAs were employed for testing mPGES1 protein staining intensity and percentage levels and both increased with clinical stage; employing a different Stage III TMA, mPGES1 intensity (not percentage) associated with reduced patient survival. Our results further show that iNOS was also highly expressed in melanoma tissues with high mPGES1 levels, and iNOS-mediated NO promoted mPGES1 expression and PGE2 production. An mPGES1specific inhibitor (CAY10526) as well as siRNA attenuated cell survival and increased apoptosis. CAY10526 significantly suppressed tumor growth and increased apoptosis in melanoma xenografts. Our findings support the value of a prognostic and predictive role for mPGES1, and suggest targeting this molecule in the PGE2 pathway as another avenue toward improving melanoma therapy.

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Oxidizing agents (e.g., H O ) cause structural and functional disruptions of molecules by affecting lipids, proteins, and nucleic acids. As a result, cellular mechanisms related to disrupted macro molecules are affected and cell death is induced. Oxidative damage can be prevented at a certain point by antioxidants or the damage can be reversed. In this work, we studied the cellular response against oxidative stress induced by H O and antioxidant-oxidant (β-carotene-H O ) interactions in terms of time, concentration, and treatment method (pre-, co-, and post) in K562 cells. We showed that co- or post-treatment with β-carotene did not protect cells from the damage of oxidative stress furthermore co- and post-β-carotene-treated oxidative stress induced cells showed similar results with only H O treated cells. However, β-carotene pre-treatment prevented oxidative damage induced by H O at concentrations lower than 1,000 μM compared with only H O -treated and co- and post-β-carotene-treated oxidative stress-induced cells in terms of studied cellular parameters (mitochondrial membrane potential [Δψ ], cell cycle and apoptosis). Prevention effect of β-carotene pre-treatment was lost at concentrations higher than 1,000 μM H O (2-10 mM). These findings suggest that β-carotene pre-treatment alters the effects of oxidative damage induced by H O and cell death processes in K562 cells.

In the present study, we aimed to evaluate the anticancer activities of Cetraria islandica (C.islandica) extracts on MCF-7 breast cancer cell lines. Cell viability, protein levels, apoptotic cells number, F-actin distribution were measured. Cell viability of MCF-7 breast cancer cells was found to be reduced in a dose-dependent manner.EC50 values of C.islandica on MCF-7 cells were found to be 9.2047 E-5 g/ml (cell amount) by using intelligence system. Expressions of p53, caspase 3 and Bcl-2, were shown to be elevated after low doses of extract and diminished after high dose treatments. PPAR- protein level was decreased, although AMP-activated kinases-α1 (AMPK-α1) protein level was increasedin its extract groups. ERK1/2 protein level was also elevated in its extract groups. 125 mg/ml of extract treated cells show a low decrease in actin filament density. MCF-7 cells with C.islandica treatment for 24 h increased the apoptotic cell percentage, though the cells-treated with C.islandica for 48 was high necrotic cells percentage. Consequently, the C.islandica extract treatment causes to elevate ERK1/2 and AMPK-α1 protein levels, resulting in PPAR- and then triggers the apoptosis by modulation caspase-3 and P53 protein levels. Therefore, C.islandica might be a good candidate for anticancer tissue, especially soft tissue tumours.