No abstract

Granulocyte colony-stimulating factor receptor (G-CSFR) has been found in placenta tissues, although its functional role has not yet been defined. In order to explore the molecular pathways induced by G-CSF in this tissue, we first reveal the presence of G-CSFR in the JEG-3 human trophoblastic cell line and then examined the phosphorylation of Janus tyrosine kinases (Jak), signal transducers and activators of transcription (STAT) proteins and mitogen-activated protein kinases (MAPK) after G-CSF binding to receptors. We showed that Jak1, Jak2, Tyk2, and STAT3 were phosphorylated after incubation with G-CSF. Phosphorylation of p38 and p44/42 MAPK was also activated by G-CSF, and specifically blocked in the presence of the corresponding inhibitors. Similar intracellular pathways were induced by G-CSF in a myeloid leukemia NFS-60 cell line that was studied in parallel. Conversely to cytokine action in myeloid cells, G-CSF did not induce a proliferative response in JEG-3 cells. When the effect of G-CSF on cellular viability was evaluated, cytokine-stimulated JEG-3 cells were protected from foetal serum starvation. In addition, when JEG-3 cells deprived of serum were incubated at different times in the presence of G-CSF, a progressive decrease in the percentage of hypodiploid cells was observed. In summary, we identified the molecular pathways activated after G-CSF binding to trophoblastic cell receptors and showed that G-CSF behaved as a protective cytokine, which supports JEG-3 cells survival.

Photodynamic therapy (PDT) is a highly specific and clinically approved method for cancer treatment in which a nontoxic drug known as photosensitizer (PS) is administered to a patient. After selective tumor irradiation, an almost complete eradication of the tumor can be reached as a consequence of reactive oxygen species (ROS) generation, which not only damage tumor cells, but also lead to tumor-associated vasculature occlusion and the induction of an immune response. Despite exhaustive investigation and encouraging results, zinc(II) phthalocyanines (ZnPcs) have not been approved as PSs for clinical use yet. This review presents an overview on the physicochemical properties of ZnPcs and biological results obtained both in vitro and in more complex models, such as 3D cell cultures, chicken chorioallantoic membranes and tumor-bearing mice. Cell death pathways induced after PDT treatment with ZnPcs are discussed in each case. Finally, combined therapeutic strategies including ZnPcs and the currently available clinical trials are mentioned.