{"id":"f3c83334-c5d0-53a2-9f72-61c78c77b6d1","stable_key":"ec987f3e-0b3c-55cc-b304-c703a738e35d:egcg-bortezomib-synergy","predicate":"potentiates","statement":"A separate 2009 KM3 myeloma-cell study reported synergistic apoptosis with EGCG plus bortezomib.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"9e087f9b-a806-5d56-b0d0-77aa268ce07c","mechanism_event_label":"Another study reported a stronger combination effect.","subject":{"id":"22e1b8eb-f35f-5afa-be20-b0534df9f6be","slug":"egcg","display_name":"Epigallocatechin-3-gallate (EGCG)","entity_type_key":"small_molecule"},"object":{"id":"23cac268-8b53-561d-beca-8d463a2ab64a","slug":"bortezomib-antitumor-effect","display_name":"Antitumor activity of bortezomib in specified models","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"9e087f9b-a806-5d56-b0d0-77aa268ce07c","stable_key":"ec987f3e-0b3c-55cc-b304-c703a738e35d:egcg-bortezomib-synergy-event","event_type":"observed_relationship","label":"Another study reported a stronger combination effect.","description":"A separate 2009 KM3 myeloma-cell study reported synergistic apoptosis with EGCG plus bortezomib.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"22e1b8eb-f35f-5afa-be20-b0534df9f6be","slug":"egcg","display_name":"Epigallocatechin-3-gallate (EGCG)","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"23cac268-8b53-561d-beca-8d463a2ab64a","slug":"bortezomib-antitumor-effect","display_name":"Antitumor activity of bortezomib in specified models","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"7c75470d-e9e0-5a6b-b342-6a1201da6b13","slug":"bortezomib","display_name":"Bortezomib","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"experimental_model","value_text":"KM3 myeloma cells; associated NF-kappaB/caspase pathway readouts.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Dose, timing and model were not harmonized with the antagonism study; no universal direction can be assigned.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"EGCG collection; comparator and shared-pathway records retain their actual intervention.","comparator":null,"unit":null,"notes":"","entity":{"slug":"egcg","display_name":"Epigallocatechin-3-gallate (EGCG)","entity_type_key":"small_molecule"}},{"dimension":"plain_language","value_text":"Another study reported a stronger combination effect.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Potentiation of (-)-epigallocatechin-3-gallate-induced apoptosis by bortezomib in multiple myeloma cells. · 2009 · https://pubmed.ncbi.nlm.nih.gov/20011976/ · DOI 10.1093/abbs/gmp094","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"c07ec48e-d6b7-5590-884f-a7b280b176e4","evidence_kind":"source_excerpt","locator":"Lines 420-426","start_line":420,"end_line":426,"excerpt":"## egcg-bortezomib-synergy\nAnother study reported a stronger combination effect.\nA separate 2009 KM3 myeloma-cell study reported synergistic apoptosis with EGCG plus bortezomib.\nModel: KM3 myeloma cells; associated NF-kappaB/caspase pathway readouts.\nLimitations: Dose, timing and model were not harmonized with the antagonism study; no universal direction can be assigned.\nEvidence access: primary abstract.\nPotentiation of (-)-epigallocatechin-3-gallate-induced apoptosis by bortezomib in multiple myeloma cells. · 2009 · https://pubmed.ncbi.nlm.nih.gov/20011976/ · DOI 10.1093/abbs/gmp094","model_system":"KM3 myeloma cells; associated NF-kappaB/caspase pathway readouts.","directness":"reported_statement","verification_status":"source_derived_draft","notes":"Primary-abstract paraphrase; no full-text methods verification claimed.","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"1f6d09e8-3aae-5c41-9ea7-15d0d1cab72d","stable_key":"import-ec987f3e-0b3c-55cc-b304-c703a738e35d","title":"EGCG: receptor signaling, metabolism, nutrient interactions and discovery questions (2026-09-18)","document_type":"imported_text","citation_label":"AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text.","file_path":"","sha256":"b101c8d4d96ee03ff97eb1922c7bb0f96943295af473fdc3ef98b0dbd62fe8c7","revision_id":"e19bc5b2-ee3c-5f67-b5c5-9dc3b7d5f850","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[{"id":"082791a9-b6ed-5e6f-9596-8df23eacd36e","title":"EGCG plus bortezomib: antagonism versus potentiation in preclinical studies","kind":"contradiction","status":"open","why":"Two 2009 studies report opposing combination outcomes, including myeloma models. They were not matched for concentration, timing or cell system, so this is an unresolved literature disagreement rather than proof of same-condition incompatibility.","resolution":"The 2011 concentration study demonstrates one boundary: high simultaneous EGCG antagonized bortezomib, whereas lower exposure did not. Reconcile original dose/order/model differences before assigning a general direction; no human efficacy or safety resolution is established.","created_at":"2026-09-18 22:58:13","record_type":"conflict","display_label":"Recorded conflict","record_url":"/conflicts/082791a9-b6ed-5e6f-9596-8df23eacd36e","sides":[{"conflict_id":"082791a9-b6ed-5e6f-9596-8df23eacd36e","ordinal":0,"label":"2009 antagonism","revision_id":"e19bc5b2-ee3c-5f67-b5c5-9dc3b7d5f850","start_line":396,"end_line":402,"quote":"## egcg-bortezomib-antagonism\nOne research group found that EGCG weakened this cancer drug.\nEGCG blocked bortezomib-mediated anticancer effects in the reported models.\nModel: Myeloma/glioblastoma cell experiments and animal models in the 2009 Blood study.\nLimitations: Preclinical findings; no human coadministration outcome trial. Chemical form and simultaneous concentrations matter.\nEvidence access: primary abstract.\nGreen tea polyphenols block the anticancer effects of bortezomib and other boronic acid-based proteasome inhibitors. · 2009 · https://pubmed.ncbi.nlm.nih.gov/19190249/ · DOI 10.1182/blood-2008-07-171389","source_key":"import-ec987f3e-0b3c-55cc-b304-c703a738e35d","source_title":"EGCG: receptor signaling, metabolism, nutrient interactions and discovery questions (2026-09-18)","claim_ids":["333063f5-aa71-5587-ae1a-070202f7a619"]},{"conflict_id":"082791a9-b6ed-5e6f-9596-8df23eacd36e","ordinal":1,"label":"2009 potentiation","revision_id":"e19bc5b2-ee3c-5f67-b5c5-9dc3b7d5f850","start_line":420,"end_line":426,"quote":"## egcg-bortezomib-synergy\nAnother study reported a stronger combination effect.\nA separate 2009 KM3 myeloma-cell study reported synergistic apoptosis with EGCG plus bortezomib.\nModel: KM3 myeloma cells; associated NF-kappaB/caspase pathway readouts.\nLimitations: Dose, timing and model were not harmonized with the antagonism study; no universal direction can be assigned.\nEvidence access: primary abstract.\nPotentiation of (-)-epigallocatechin-3-gallate-induced apoptosis by bortezomib in multiple myeloma cells. · 2009 · https://pubmed.ncbi.nlm.nih.gov/20011976/ · DOI 10.1093/abbs/gmp094","source_key":"import-ec987f3e-0b3c-55cc-b304-c703a738e35d","source_title":"EGCG: receptor signaling, metabolism, nutrient interactions and discovery questions (2026-09-18)","claim_ids":["f3c83334-c5d0-53a2-9f72-61c78c77b6d1"]},{"conflict_id":"082791a9-b6ed-5e6f-9596-8df23eacd36e","ordinal":2,"label":"2011 high-exposure boundary","revision_id":"e19bc5b2-ee3c-5f67-b5c5-9dc3b7d5f850","start_line":428,"end_line":434,"quote":"## egcg-bortezomib-high\nA follow-up found antagonism at very high simultaneous exposure.\nIn CWR22 xenografts, EGCG above 200 micromolar at bortezomib administration abolished measured antitumor activity.\nModel: Immunocompromised mice; bortezomib 0.8 mg/kg IV twice weekly.\nLimitations: Concentration-specific animal findings do not establish a human safety threshold.\nEvidence access: primary abstract.\nPreclinical evaluation of the antitumor activity of bortezomib in combination with vitamin C or with epigallocatechin gallate, a component of green tea. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21400028/ · DOI 10.1007/s00280-011-1591-2","source_key":"import-ec987f3e-0b3c-55cc-b304-c703a738e35d","source_title":"EGCG: receptor signaling, metabolism, nutrient interactions and discovery questions (2026-09-18)","claim_ids":["ba14be51-ba3e-5e12-91d2-e1e0ffc3dfaa"]},{"conflict_id":"082791a9-b6ed-5e6f-9596-8df23eacd36e","ordinal":3,"label":"2011 lower-exposure comparison","revision_id":"e19bc5b2-ee3c-5f67-b5c5-9dc3b7d5f850","start_line":436,"end_line":442,"quote":"## egcg-bortezomib-lower\nThe drug interaction was not identical at every concentration.\nAt EGCG 11–16 micromolar, the same model showed no antagonism; tumor-growth inhibition was 63.5% versus 53.9–58.9% with bortezomib alone.\nModel: CWR22 xenograft exposure comparison.\nLimitations: Not proof of clinical synergy or unrestricted safe coadministration.\nEvidence access: primary abstract.\nPreclinical evaluation of the antitumor activity of bortezomib in combination with vitamin C or with epigallocatechin gallate, a component of green tea. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21400028/ · DOI 10.1007/s00280-011-1591-2","source_key":"import-ec987f3e-0b3c-55cc-b304-c703a738e35d","source_title":"EGCG: receptor signaling, metabolism, nutrient interactions and discovery questions (2026-09-18)","claim_ids":["c5f839a2-f298-5fbd-ad7f-99d91199de2a"]}]}],"corrections":[],"research":null}