| Features: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Polyphenol found in fruits, vegetables, nuts and some mushrooms. Strawberries, raspberries, blackberries, cherries and walnuts, green tea and red wine. Pomegranate arils are a well known source. Ellagic acid (EA) is a dietary polyphenol found in berries and pomegranate-related foods, with reported anti-inflammatory (NF-κB↓), survival-pathway suppression (PI3K/AKT↓), and anti-proliferative effects including G1 arrest and apoptosis in many cancer models. A key practical nuance is that EA/ellagitannins are extensively transformed by gut microbiota into urolithins, which are more bioavailable and may account for a large share of systemic effects. - Ellagitannins are high molecular weight polyphenols with a complex structure that includes one or more HHDP groups attached to a sugar. - Ellagic Acid is the simpler, bioactive compound released when the HHDP groups in ellagitannins cyclize during hydrolysis. - one best source is raspberries. 100g gives ~50mg(reasonable dose) - Ellagic acid has very poor oral bioavailability - Peak plasma EA after high oral intake is typically: <50–100 nM, often much lower, this is far below concentrations used in many in-vitro anticancer studies (5–50 µM). - efficacy depends on gut metabolism (ie ability to produce Urolithin A) - also look at Urolithin supplements Pathways: Apoptosis Regulation: (Bax, Bad) (Bcl-2, Bcl-xL) Cell Cycle Arrest: G0/G1 or G2/M phases) NF-κB (inhibit): MAPK Pathways: (including ERK1/2, JNK, and p38 MAPK) PI3K/Akt/mTOR: might downregulate this pathway p53 Pathway: may influence the expression or activation of p53 Oxidative Stress and Nrf2 Pathway:exhibits antioxidant properties, Summary: - Anti-oxidant and metal chelating - with some evidence it can induce ROS in cancer tumor conditions (mitochondrial stress, redox-unstable cells) - reported synergy with Curcumin - Reported, reduced the viability of cancer cells at a concentration of 10 µmol/L, while in healthy cells, this effect was observed only at a concentration of 200 µmol/L - Pomegranate juice (PJ) (180 ml) containing EA (25 mg) and ETs (318 mg, as punicalagins, the major fruit ellagitannin). Plasma concentration (31.9 ng/ml) after 1 h post-ingestion but was rapidly eliminated by 4 h. (Hence might be difficult to consume enough EA!!!! to match vitro requirements) - Increased the expression of p53 and p21 proteins as well as markers of apoptosis (Bax and caspase-3), and decreases Bcl-2, NF-кB, and iNOS - EA has restricted bioavailability, primarily due to its hydrophobic nature and very low water solubility. - Processing methods can alter EA content; peel extraction often increases measured EA, while prolonged storage/freezing may reduce levels. Total ellagic acid equivalents (free + bound). Punica granatum L. Pomegranate 700mg/kg (arils), 38700mg/kg(mesocarp) Rubus idaeus L. Raspberry 2637–3309mg/kg jaglandaceae Walnut 410mg/kg(freeEA) 8230mg/kg(totalEA)
Time-Scale Flag (TSF): P / R / G
|
| 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. |
| 1605- | EA, | Ellagic Acid and Cancer Hallmarks: Insights from Experimental Evidence |
| - | Review, | Var, | 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#:74 Target#:38 State#:% Dir#:4
wNotes=0 sortOrder:rid,rpid