| Features: | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Iron plays a dual and highly context-dependent role in cancer biology. It is essential for tumor proliferation due to its requirement in DNA synthesis (ribonucleotide reductase), mitochondrial respiration, and cell cycle progression. Many cancers exhibit increased iron uptake (↑ transferrin receptor, TfR1) and decreased iron export (↓ ferroportin), leading to intracellular iron accumulation that supports rapid growth. However, excess labile iron also promotes oxidative stress through Fenton chemistry (Fe²⁺ + H₂O₂ → •OH), contributing to DNA damage and genomic instability. A major therapeutic concept is ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation. Tumors with high iron dependency can be selectively vulnerable to ferroptosis induction. Conversely, chronic iron overload may promote tumor initiation through ROS-mediated mutagenesis and inflammatory signaling. Thus, iron sits at a metabolic intersection: -Pro-tumor when supporting proliferation and ROS-driven mutation -Anti-tumor when leveraged to trigger ferroptotic cell death Iron biology in cancer is best understood through three axes: -Iron uptake/storage/export balance -ROS and oxidative stress dynamics -Ferroptosis susceptibilityIron is a vital trace element that plays essential roles in various physiological processes. Its importance stems from its involvement in oxygen transport, energy production, DNA synthesis, and numerous enzymatic reactions. – Iron is a critical component of hemoglobin in red blood cells, enabling the binding and transport of oxygen from the lungs to tissues. – Iron participates in redox reactions due to its ability to alternate between ferrous (Fe²⁺) and ferric (Fe³⁺) states. Tumor cells often require increased iron to support their rapid proliferation and metabolic demands. – Elevated iron availability can promote DNA synthesis, cell division, and tumor growth. • Promotion of Reactive Oxygen Species (ROS) Formation: – Iron’s redox-active nature, while important for normal cell functions, can also lead to the generation of reactive oxygen species via reactions such as the Fenton reaction: Fe²⁺ + H₂O₂ → Fe³⁺ + •OH + OH⁻ – The hydroxyl radicals (•OH) produced are highly reactive and can cause oxidative damage to cellular components (DNA, proteins, lipids). – This oxidative damage may contribute to genomic instability, mutations, and the progression of cancer. Cancer cells often exhibit increased iron dependency, targeting iron metabolism is a strategy that is being explored for cancer therapy. – Approaches include the use of iron chelators to sequester iron and limit its availability to tumor cells, thereby inhibiting their growth. – Alternatively, therapies may aim to exploit iron’s capacity to generate toxic ROS beyond a threshold that cancer cells can manage, leading to selective cell death. Iron (Fe) – Cancer Pathway Matrix
Time-Scale Flag (TSF): |
| Source: |
| Type: |
| In all eukaryotic cells, intracellular Ca2+ levels are maintained at low resting concentrations (approximately 100 nM) by the activity of the major Ca2+ extrusion system, the plasma membrane Ca2+-ATPase (PMCA), which exchanges extracellular protons (H+) for cytosolic Ca2+. Indeed, sustained elevation of [Ca2+]C in the form of overload, saturating all Ca2+-dependent effectors, prolonged decrease in [Ca2+]ER, causing ER stress response, and high [Ca2+]M, inducing mitochondrial permeability transition (MPT), are considered to be pro-death factors. In cancer the Ca2+-handling toolkit undergoes profound remodelling (figure 1) to favour activation of Ca2+-dependent transcription factors, such as the nuclear factor of activated T cells (NFAT), c-Myc, c-Jun, c-Fos that promote hypertrophic growth via induction of the expression of the G1 and G1/S phase transition cyclins (D and E) and associated cyclin-dependent kinases (CDK4 and CDK2). Thus, cancer cells may evade apoptosis through decreasing calcium influx into the cytoplasm. This can be achieved by either downregulation of the expression of plasma membrane Ca2+-permeable ion channels or by reducing the effectiveness of the signalling pathways that activate these channels. Such protective measures would largely diminish the possibility of Ca2+ overload in response to pro-apoptotic stimuli, thereby impairing the effectiveness of mitochondrial and cytoplasmic apoptotic pathways. Voltage-Gated Calcium Channels (VGCCs): Overexpression of VGCCs has been associated with increased tumor growth and metastasis in various cancers, including breast and prostate cancer. Store-Operated Calcium Entry (SOCE): SOCE mechanisms, such as STIM1 and ORAI1, are often upregulated in cancer cells, contributing to enhanced cell survival and proliferation. High intracellular calcium levels are associated with increased cell proliferation and migration, leading to a poorer prognosis. Calcium signaling can also influence hormone receptor status, affecting treatment responses. Increased Ca²⁺ signaling is associated with advanced disease and metastasis. Patients with higher CaSR expression may have a worse prognosis due to enhanced tumor growth and resistance to apoptosis. -Ca2+ is an important regulator of the electric charge distribution of bio-membranes. |
| 1762- | MF, | Fe, | Triggering the apoptosis of targeted human renal cancer cells by the vibration of anisotropic magnetic particles attached to the cell membrane |
| - | in-vitro, | RCC, | NA |
Query results interpretion may depend on "conditions" listed in the research papers. Such Conditions may include : -low or high Dose -format for product, such as nano of lipid formations -different cell line effects -synergies with other products -if effect was for normal or cancerous cells
Filter Conditions: Pro/AntiFlg:% IllCat:% CanType:% Cells:% prod#:104 Target#:38 State#:% Dir#:2
wNotes=0 sortOrder:rid,rpid