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: Sarah-Jane Cozzi, Thuy T Le, Steven M Ogbourne, Cini James, Andreas Suhrbier
• Journal: Archives of dermatological research (Arch Dermatol Res) Vol. 305 Issue 1 Pg. 79-83 (Jan 2013) ISSN: 1432-069X [Electronic] Germany
• PMID: 22871992 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 3-ingenyl angelate
• Antineoplastic Agents
• Diterpenes
• Gels

Topics

• Administration, Cutaneous
• Animals
• Antineoplastic Agents (administration & dosage, pharmacology)
• Carcinoma, Squamous Cell (drug therapy, immunology, ultrastructure)
• Diterpenes (administration & dosage, pharmacology)
• Female
• Gels
• Male
• Mice
• Mice, Hairless
• Microscopy, Electron
• Mitochondria (drug effects, pathology)
• Mitochondrial Swelling (drug effects)
• Necrosis
• Neutrophil Infiltration (drug effects)
• Skin Neoplasms (drug therapy, immunology, ultrastructure)
• Time Factors