Annexin A1 (ANXA1) is the first characterized member of the annexins superfamily. It binds the cellular membrane phospholipids in Ca(2+) regulated manner. Annexin A1 has been found in several tissues and many physiological roles as hormones secretion, vesiculation, inflammatory response, apoptosis and differentiation have been shown. Its subcellular localization and binding with many partner proteins are altered accordingly with its physiological role. The Annexin A1 membrane localization is crucial for binding to receptors, suggesting a paracrine and juxtacrine extracellular action. Annexin A1 is subjected to several post-translational modifications. In particular the protein is phosphorylated on several residues both on the N-terminal functional domain and on the C-terminus core. Different kinases have been identified as responsible for the phosphorylation status of selective residues. The specific change in the phosphorylation status on the different sites alters ANXA1 localization, binding properties and functions. This review shows the physiological relevance of the ANXA1 phosphorylation leading to the conclusion that numerous and different roles of Annexin A1 could be associated with different phosphorylations to alter not only intracellular localization and bindings to its partners but also the extracellular receptor interactions.

In this study we investigated effects of natural extract from the black tea Camellia sinensis (BTE) against human colon carcinoma cell line HT-29, human breast carcinoma cell line MCF-7, human alveolar carcinoma cell line A549 and healthy cell line NIH-3T3. We identified concentration range for cytotoxic/antiproliferative effects using MTT assay and the trypan blue assay, gel electrophoresis we employed to determine the type of cell death induced by BTE and DNA damage we determined by comet assay. Different concentrations of the extract (0.00078 - 5 μg/mL) we added to the cultured cells and incubated for 216 h. BTE showed cytotoxic effects against all carcinoma cell lines, however HT-29 and MCF-7 cells were more sensitive than A549. BTE showed no antiproliferative effect against healthy cells NIH-3T3 at tested concentrations. We found no apoptotic cell death in HT-29 and MCF-7 cells after 72 h of incubation in case of single administration of BTE but in case of repetitive administration of BTE (BTE was added to the cells each day) we found apoptotic cell death in HT-29 after 72 h incubation. BTE induced also DNA strand breaks and oxidative damage to DNA in carcinoma cells HT-29 and MCF-7.