title: Effective treatment of squamous cell carcinomas with ingenol mebutate gel in immunologically intact SKH1 mice.
abstract: Ingenol mebutate has recently been approved by the Federal Drug Administration (USA) as a topical treatment for actinic keratoses. Herein, we describe the efficacy of ingenol mebutate for the topical treatment of squamous cell carcinoma (SCC) using a wild-type mouse model (SKH1) and the UV-induced mouse SCC cell line, T7. Daily treatment for 2 days with 0.25 % ingenol mebutate gel produced a cure rate of 70 %, with 0 % for placebo gel. Electron microscopy revealed swelling of cancer cell mitochondria within 1 h, with disruption of the inner mitochondrial membranes evident at 6 h post treatment. Primary necrosis of cancer cells was clearly evident by 24 h. Treatment was associated with local haemorrhage and a prodigious neutrophil infiltrate, with anti-T7 antibodies also detected. This is the first report of the successful treatment of SCC tumours with ingenol mebutate gel in wild-type mice, and supports the view that ingenol mebutate induces primary necrosis and activates the immune system.
authors.affiliation: Queensland Institute of Medical Research, Post Office Royal Brisbane Hospital, Brisbane, QLD, 4029, Australia.|Peplin Ltd, Brisbane, QLD, Australia.
authors.forename: Sarah-Jane
authors.initials: SJ
authors.lastname: Cozzi
authors.affiliation: Queensland Institute of Medical Research, Post Office Royal Brisbane Hospital, Brisbane, QLD, 4029, Australia.
authors.forename: Thuy T
authors.initials: TT
authors.lastname: Le
authors.affiliation: Peplin Ltd, Brisbane, QLD, Australia.|University of the Sunshine Coast, Maroochydore, QLD, 4558, Australia.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Ogbourne
authors.affiliation: Queensland Institute of Medical Research, Post Office Royal Brisbane Hospital, Brisbane, QLD, 4029, Australia.
authors.forename: Cini
authors.initials: C
authors.lastname: James
authors.affiliation: Queensland Institute of Medical Research, Post Office Royal Brisbane Hospital, Brisbane, QLD, 4029, Australia. andreasS@qimr.edu.au.|Griffith University, Nathan, QLD, 4111, Australia. andreasS@qimr.edu.au.
authors.forename: Andreas
authors.initials: A
authors.lastname: Suhrbier
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000276:immunology / Q000648:ultrastructure; D004224:Diterpenes / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D005782:Gels; D008297:Male; D051379:Mice; D008812:Mice, Hairless; D008854:Microscopy, Electron; D008928:Mitochondria / Q000187:drug effects / Q000473:pathology; D008933:Mitochondrial Swelling / Q000187:drug effects; D009336:Necrosis; D020556:Neutrophil Infiltration / Q000187:drug effects; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000648:ultrastructure; D013997:Time Factors
chemical_list: C486592:3-ingenyl angelate; D000970:Antineoplastic Agents; D004224:Diterpenes; D005782:Gels