{"id":"3b7e7cf5-9103-5282-9bc5-933897ae1da3","stable_key":"cb568d28-484a-5c2e-9fcc-2d780358e514:c-reg-ferritin-heavy-protects","predicate":"overexpression-protects","statement":"Ferritin-heavy-chain overexpression in H1299 cells lowered labile iron and increased clonogenic survival after pharmacological ascorbate, supporting a protective role of intracellular iron sequestration in this setting.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"8d2685b7-3f11-52ea-8f3f-dacf0f0da8bc","mechanism_event_label":"Locking more iron into ferritin protected these lung cancer cells from the exposure.","subject":{"id":"05e98c8a-c341-5856-971a-5a7001db7fed","slug":"fth1","display_name":"Ferritin heavy chain","entity_type_key":"protein"},"object":{"id":"2df681bd-e107-5041-8c91-3c127c6731e1","slug":"cancer-cell-clonogenic-survival","display_name":"Cancer-cell clonogenic survival","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"8d2685b7-3f11-52ea-8f3f-dacf0f0da8bc","stable_key":"cb568d28-484a-5c2e-9fcc-2d780358e514:c-reg-ferritin-heavy-protects-event","event_type":"biochemical_relationship","label":"Locking more iron into ferritin protected these lung cancer cells from the exposure.","description":"Ferritin-heavy-chain overexpression in H1299 cells lowered labile iron and increased clonogenic survival after pharmacological ascorbate, supporting a protective role of intracellular iron sequestration in this setting.","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":"d1a76588-8d56-5ba9-9fd1-16a82dc52b94","slug":"labile-cellular-iron","display_name":"Cellular labile iron pool","entity_type_key":"chemical_species"},"role":"decreased reactive pool","stoichiometry":null,"state_label":"","sequence_order":1,"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":2,"notes":""},{"entity":{"id":"5ee66abb-7d76-5b09-bd06-77d39d0e3bcd","slug":"mammalian-ferritin","display_name":"Mammalian ferritin protein complexes","entity_type_key":"protein_family"},"role":"protein-complex context","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"05e98c8a-c341-5856-971a-5a7001db7fed","slug":"fth1","display_name":"Ferritin heavy chain","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""},{"entity":{"id":"2df681bd-e107-5041-8c91-3c127c6731e1","slug":"cancer-cell-clonogenic-survival","display_name":"Cancer-cell clonogenic survival","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 6I–L","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"H1299 adenoviral ferritin-heavy-chain versus empty-vector cultures; calcein/BIP and clonogenic assays","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"20-MOI ferritin-heavy-chain expression 36 h before experiment; 5 pmol/cell (approximately 2–3 mM) ascorbate for 1 h.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Engineered overexpression is not dietary iron deficiency or ordinary ferritin concentration; serum ferritin does not measure this intracellular intervention.","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":"Locking more iron into ferritin protected these lung cancer cells from the exposure.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[c-reg-schoenfeld] O2⋅- and H2O2-Mediated Disruption of Fe Metabolism Causes the Differential Susceptibility of NSCLC and GBM Cancer Cells to Pharmacological Ascorbate. (2017). https://pubmed.ncbi.nlm.nih.gov/28366679/ DOI: 10.1016/j.ccell.2017.02.018","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"NSCLC cells","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"d3902447-8c77-5f1c-8c00-af763e753dc0","evidence_kind":"source_excerpt","locator":"Lines 1369-1381","start_line":1369,"end_line":1381,"excerpt":"### c-reg-ferritin-heavy-protects\nFerritin-heavy-chain overexpression in H1299 cells lowered labile iron and increased clonogenic survival after pharmacological ascorbate, supporting a protective role of intracellular iron sequestration in this setting.\nCondition category: normal\nnutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Locking more iron into ferritin protected these lung cancer cells from the exposure.\norganism: Homo sapiens\ntissue_or_cell_type: NSCLC cells\nexperimental_model: H1299 adenoviral ferritin-heavy-chain versus empty-vector cultures; calcein/BIP and clonogenic assays\nlimitations: Engineered overexpression is not dietary iron deficiency or ordinary ferritin concentration; serum ferritin does not measure this intracellular intervention.\nexposure: 20-MOI ferritin-heavy-chain expression 36 h before experiment; 5 pmol/cell (approximately 2–3 mM) ascorbate for 1 h.\ncross_nutrient: true\nevidence_location: Figure 6I–L\n[c-reg-schoenfeld] O2⋅- and H2O2-Mediated Disruption of Fe Metabolism Causes the Differential Susceptibility of NSCLC and GBM Cancer Cells to Pharmacological Ascorbate. 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