{"id":"06ee1896-3186-57e1-8fb7-2bacb8715d50","stable_key":"cb568d28-484a-5c2e-9fcc-2d780358e514:c-reg-lymphoma-extracellular-ascorbate","predicate":"induces-extracellular-exposure-dependent","statement":"JLP-119 lymphoma cells died after extracellular ascorbate exposure even when previously loaded to about 3 mM intracellular ascorbate; matched loading through dehydroascorbic acid did not reproduce the extracellular-ascorbate death effect.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"544be487-a6b1-5e60-b751-c131907b34fc","mechanism_event_label":"The killing depended on vitamin C outside these lymphoma cells, not merely on having vitamin C inside them.","subject":{"id":"38d0c4d9-53d1-5239-bfe3-c1b5e9b79085","slug":"ascorbate","display_name":"L-Ascorbate","entity_type_key":"small_molecule"},"object":{"id":"9401b468-dcb1-5289-bcc8-6939ded7d4e5","slug":"lymphoma-cell-death","display_name":"Lymphoma cell death","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"544be487-a6b1-5e60-b751-c131907b34fc","stable_key":"cb568d28-484a-5c2e-9fcc-2d780358e514:c-reg-lymphoma-extracellular-ascorbate-event","event_type":"biochemical_relationship","label":"The killing depended on vitamin C outside these lymphoma cells, not merely on having vitamin C inside them.","description":"JLP-119 lymphoma cells died after extracellular ascorbate exposure even when previously loaded to about 3 mM intracellular ascorbate; matched loading through dehydroascorbic acid did not reproduce the extracellular-ascorbate death effect.","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":"e6658c2b-ccff-5122-80a5-2e153f12ba90","slug":"dehydroascorbic-acid","display_name":"Dehydroascorbic acid","entity_type_key":"small_molecule"},"role":"comparison loading reagent","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"da9d64bc-69d4-5d97-90a4-8f0ed03e0ac8","slug":"hydrogen-peroxide","display_name":"Hydrogen peroxide","entity_type_key":"small_molecule"},"role":"downstream oxidant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"38d0c4d9-53d1-5239-bfe3-c1b5e9b79085","slug":"ascorbate","display_name":"L-Ascorbate","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"9401b468-dcb1-5289-bcc8-6939ded7d4e5","slug":"lymphoma-cell-death","display_name":"Lymphoma cell death","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""}]},"contexts":[{"dimension":"cross_nutrient","value_text":"false","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"evidence_location","value_text":"Figure 2D–E","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Human JLP-119 Burkitt lymphoma culture; 1-h exposure, washing, Hoechst/propidium iodide cell-death assessment after 18–22 h","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Fresh L-ascorbic acid neutralized to pH 7.0; 2 mM extracellular ascorbate for 1 h; cells 2.5 × 10^5/mL in serum-containing culture medium.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Pharmacological in-vitro exposure; medium chemistry and peroxide clearance differ from intact tissues. No dietary or clinical anticancer inference. This conclusion is specific to this line and loading protocol.","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":"The killing depended on vitamin C outside these lymphoma cells, not merely on having vitamin C inside them.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[c-reg-chen] Pharmacologic ascorbic acid concentrations selectively kill cancer cells: action as a pro-drug to deliver hydrogen peroxide to tissues. (2005). https://pubmed.ncbi.nlm.nih.gov/16157892/ DOI: 10.1073/pnas.0506390102","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Burkitt lymphoma cells","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"8e9c7027-4721-5b7d-90cd-8179a64dc3f7","evidence_kind":"source_excerpt","locator":"Lines 1229-1241","start_line":1229,"end_line":1241,"excerpt":"### c-reg-lymphoma-extracellular-ascorbate\nJLP-119 lymphoma cells died after extracellular ascorbate exposure even when previously loaded to about 3 mM intracellular ascorbate; matched loading through dehydroascorbic acid did not reproduce the extracellular-ascorbate death effect.\nCondition category: normal\nnutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: The killing depended on vitamin C outside these lymphoma cells, not merely on having vitamin C inside them.\norganism: Homo sapiens\ntissue_or_cell_type: Burkitt lymphoma cells\nexperimental_model: Human JLP-119 Burkitt lymphoma culture; 1-h exposure, washing, Hoechst/propidium iodide cell-death assessment after 18–22 h\nlimitations: Pharmacological in-vitro exposure; medium chemistry and peroxide clearance differ from intact tissues. No dietary or clinical anticancer inference. This conclusion is specific to this line and loading protocol.\nexposure: Fresh L-ascorbic acid neutralized to pH 7.0; 2 mM extracellular ascorbate for 1 h; cells 2.5 × 10^5/mL in serum-containing culture medium.\ncross_nutrient: false\nevidence_location: Figure 2D–E\n[c-reg-chen] Pharmacologic ascorbic acid concentrations selectively kill cancer cells: action as a pro-drug to deliver hydrogen peroxide to tissues. (2005). https://pubmed.ncbi.nlm.nih.gov/16157892/ DOI: 10.1073/pnas.0506390102","model_system":"Human JLP-119 Burkitt lymphoma culture; 1-h exposure, washing, Hoechst/propidium iodide cell-death assessment after 18–22 h","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [c-reg-chen] Pharmacologic ascorbic acid concentrations selectively kill cancer cells: action as a pro-drug to deliver hydrogen peroxide to tissues. (2005). https://pubmed.ncbi.nlm.nih.gov/16157892/ DOI: 10.1073/pnas.0506390102","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"fa811221-13bd-5c10-adc1-eaf097c7703c","stable_key":"import-cb568d28-484a-5c2e-9fcc-2d780358e514","title":"Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17)","document_type":"imported_text","citation_label":"AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text.","file_path":"","sha256":"b7fd83f956abb81855f2ea23199ba14e465cd91f4a2ac560277ec21ddafd7bfc","revision_id":"6cde9bbb-d712-5746-82a6-85b144253efa","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}