{"id":"4892440b-7844-5f76-a37a-16330d9ea485","stable_key":"cb568d28-484a-5c2e-9fcc-2d780358e514:c-reg-extracellular-iron-cytoprotection","predicate":"reduces-ascorbate-induced-loss-of","statement":"Supplementing RPMI/FCS with as little as 5 µM iron as FAC prevented the marked viability loss caused by 5–10 mM ascorbate in LNCaP and PC-3 cultures; protection also occurred at higher tested iron additions.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"94003f74-5c1c-552b-9907-6178b1061772","mechanism_event_label":"In this medium, extra iron protected the prostate cancer cells from high-concentration vitamin C.","subject":{"id":"80537c07-6aa7-5a3b-9148-f7033ce3c0fd","slug":"ferric-ammonium-citrate","display_name":"Ferric ammonium citrate","entity_type_key":"chemical_species"},"object":{"id":"c5c8bbb1-0374-5f02-ac5a-e8b7f3b0c95f","slug":"prostate-cell-viability","display_name":"Prostate cancer-cell viability","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"94003f74-5c1c-552b-9907-6178b1061772","stable_key":"cb568d28-484a-5c2e-9fcc-2d780358e514:c-reg-extracellular-iron-cytoprotection-event","event_type":"biochemical_relationship","label":"In this medium, extra iron protected the prostate cancer cells from high-concentration vitamin C.","description":"Supplementing RPMI/FCS with as little as 5 µM iron as FAC prevented the marked viability loss caused by 5–10 mM ascorbate in LNCaP and PC-3 cultures; protection also occurred at higher tested iron additions.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"da1a7137-08f2-5a36-8bb6-377fbd32e327","slug":"vitamin-c","display_name":"Vitamin C","entity_type_key":"chemical_species"},"role":"nutrient context","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"38d0c4d9-53d1-5239-bfe3-c1b5e9b79085","slug":"ascorbate","display_name":"L-Ascorbate","entity_type_key":"small_molecule"},"role":"challenge","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"964be7ac-43bd-5f3e-8326-94f0590de67a","slug":"iron-iii","display_name":"Ferric iron","entity_type_key":"ion"},"role":"supplied iron oxidation state","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"da9d64bc-69d4-5d97-90a4-8f0ed03e0ac8","slug":"hydrogen-peroxide","display_name":"Hydrogen peroxide","entity_type_key":"small_molecule"},"role":"mechanistic mediator","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"80537c07-6aa7-5a3b-9148-f7033ce3c0fd","slug":"ferric-ammonium-citrate","display_name":"Ferric ammonium citrate","entity_type_key":"chemical_species"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""},{"entity":{"id":"c5c8bbb1-0374-5f02-ac5a-e8b7f3b0c95f","slug":"prostate-cell-viability","display_name":"Prostate cancer-cell viability","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":5,"notes":""}]},"contexts":[{"dimension":"cross_nutrient","value_text":"true","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"evidence_location","value_text":"Figure 1a–b; treatment Methods","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Human LNCaP and PC-3 monolayers in RPMI-1640 +10% FCS; MTT and crystal-violet viability assays","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"5 or 10 mM freshly neutralized ascorbic acid, 2 h, then wash/recovery; FAC adds 5–30 µM iron to medium containing 5.6 ±1.3 µM total iron.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"FAC supplementation changes iron speciation as well as concentration; matching plasma total iron does not reconstruct transferrin binding or tissue interstitial chemistry. No clinical efficacy conclusion.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Vitamin C research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"vitamin-c","display_name":"Vitamin C","entity_type_key":"chemical_species"}},{"dimension":"organism","value_text":"Homo sapiens","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"In this medium, extra iron protected the prostate cancer cells from high-concentration vitamin C.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[c-reg-mojic] Extracellular iron diminishes anticancer effects of vitamin C: an in vitro study. (2014). https://pubmed.ncbi.nlm.nih.gov/25092529/ DOI: 10.1038/srep05955","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Prostate carcinoma cells","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"c44cd21b-5e88-53ae-a940-ba27ac0129b1","evidence_kind":"source_excerpt","locator":"Lines 1285-1297","start_line":1285,"end_line":1297,"excerpt":"### c-reg-extracellular-iron-cytoprotection\nSupplementing RPMI/FCS with as little as 5 µM iron as FAC prevented the marked viability loss caused by 5–10 mM ascorbate in LNCaP and PC-3 cultures; protection also occurred at higher tested iron additions.\nCondition category: normal\nnutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: In this medium, extra iron protected the prostate cancer cells from high-concentration vitamin C.\norganism: Homo sapiens\ntissue_or_cell_type: Prostate carcinoma cells\nexperimental_model: Human LNCaP and PC-3 monolayers in RPMI-1640 +10% FCS; MTT and crystal-violet viability assays\nlimitations: FAC supplementation changes iron speciation as well as concentration; matching plasma total iron does not reconstruct transferrin binding or tissue interstitial chemistry. No clinical efficacy conclusion.\nexposure: 5 or 10 mM freshly neutralized ascorbic acid, 2 h, then wash/recovery; FAC adds 5–30 µM iron to medium containing 5.6 ±1.3 µM total iron.\ncross_nutrient: true\nevidence_location: Figure 1a–b; treatment Methods\n[c-reg-mojic] Extracellular iron diminishes anticancer effects of vitamin C: an in vitro study. (2014). https://pubmed.ncbi.nlm.nih.gov/25092529/ DOI: 10.1038/srep05955","model_system":"Human LNCaP and PC-3 monolayers in RPMI-1640 +10% FCS; MTT and crystal-violet viability assays","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [c-reg-mojic] Extracellular iron diminishes anticancer effects of vitamin C: an in vitro study. 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