Itaconate and itaconate derivatives target JAK1 to suppress alternative activation of macrophages.

The Krebs cycle-derived metabolite itaconate and its derivatives suppress the inflammatory response in pro-inflammatory "M1" macrophages. However, alternatively activated "M2" macrophages can take up itaconate. We therefore examined the effect of itaconate and 4-octyl itaconate (OI) on M2 macrophage activation.

Genome-wide analysis of copy number alterations led to the characterisation of PDCD10 as oncogene in ovarian cancer.

Copy Number Alterations (CNAs) represent the most common genetic alterations identified in ovarian cancer cells, being responsible for the extensive genomic instability observed in this cancer. Here we report the identification of CNAs in a cohort of Italian patients affected by ovarian cancer performed by SNP-based array. Our analysis allowed the identification of 201 significantly altered chromosomal bands (70 copy number gains; 131 copy number losses).

Ferroptosis and Cancer: Mitochondria Meet the "Iron Maiden" Cell Death.

Ferroptosis is a new type of oxidative regulated cell death (RCD) driven by iron-dependent lipid peroxidation. As major sites of iron utilization and master regulators of oxidative metabolism, mitochondria are the main source of reactive oxygen species (ROS) and, thus, play a role in this type of RCD. Ferroptosis is, indeed, associated with severe damage in mitochondrial morphology, bioenergetics, and metabolism.

FtH-Mediated ROS Dysregulation Promotes CXCL12/CXCR4 Axis Activation and EMT-Like Trans-Differentiation in Erythroleukemia K562 Cells.

The cell-microenvironment communication is essential for homing of hematopoietic stem cells in stromal niches. Recent evidences support the involvement of epithelial-to-mesenchymal (EMT) process in hematopoietic stem cell homeostasis as well as in leukemia cells invasiveness and migration capability. Here, we demonstrate that the alteration of iron homeostasis and the consequent increase of redox metabolism, mediated by the stable knock down of ferritin heavy chain (FtH), enhances the expression of CXCR4 in K562 erythroleukemia cells, thus promoting CXCL12-mediated motility.

H-Ferritin Affects Cisplatin-Induced Cytotoxicity in Ovarian Cancer Cells through the Modulation of ROS.

Reactive oxygen species (ROS) mediates cisplatin-induced cytotoxicity in tumor cells. However, when cisplatin-induced ROS do not reach cytotoxic levels, cancer cells may develop chemoresistance. This phenomenon can be attributed to the inherited high expression of antioxidant protein network.

Chemoresistance in H-Ferritin Silenced Cells: The Role of NF-κB.

Nuclear Factor-κB (NF-κB) is frequently activated in tumor cells contributing to aggressive tumor growth and resistance to chemotherapy. Here we demonstrate that Ferritin Heavy Chain (FHC) protein expression inversely correlates with NF-κB activation in cancer cell lines. In fact, FHC silencing in K562 and SKOV3 cancer cell lines induced p65 nuclear accumulation, whereas FHC overexpression correlated with p65 nuclear depletion in the same cell lines.