Vitamin E analog, alpha-tocopherol ether-linked acetic acid analog, alone and in combination with celecoxib, reduces multiplicity of ultraviolet-induced skin cancers in mice.

Abstract

The goals of this study were to determine whether alpha-tocopherol ether-linked acetic acid analog (alpha-TEA), a novel vitamin E analog, and celecoxib, alone or in combination, when administered as a late intervention can reduce the ultraviolet-induced nonmelanoma skin-tumor burden of established tumors, prevent additional tumors from developing, and prevent tumor recurrence once treatments are stopped. Hairless SKH-1 female mice were ultraviolet-irradiated for 24 weeks, divided into treatment groups so that each group had approximately 5.8 tumors/mouse, and then treated with 72 mug of liposome-formulated alpha-TEA by aerosol inhalation, 500 p.p.m. celecoxib in AIN-76 A diet, or a combination of alpha-TEA and celecoxib for 4 weeks. At the end of 4 weeks of treatment, each treatment group was subdivided, with one subgroup continuing to receive treatment and with treatment being stopped in the other. Skin-tumor development was monitored visually throughout the study and by histologic evaluation at the end. After 4 weeks of treatment, all treatments showed statistically significant reductions in tumor number when compared with controls. After termination of treatment, only alpha-TEA prevented a significant increase in tumor recurrence; however, continuous combination treatment resulted in the lowest total number of tumors. In conclusion alpha-TEA is an effective late-stage chemopreventive agent for nonmelanoma skin cancer that exhibits lasting benefits.

• Authors: Shelley B Riedel, Susan M Fischer, Bob G Sanders, Kimberly Kline
• Journal: Anti-cancer drugs (Anticancer Drugs) Vol. 19 Issue 2 Pg. 175-81 (Feb 2008) ISSN: 0959-4973 [Print] England
• PMID: 18176114 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Acetates
• Cyclooxygenase Inhibitors
• Liposomes
• Pyrazoles
• Sulfonamides
• Celecoxib
• 2,5,7,8-tetramethyl-2R-(4R,8R,12-trimethyltridecyl)chroman-6-yloxy acetic acid
• Tocopherols

Topics

• Acetates (chemistry)
• Administration, Inhalation
• Animals
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Carcinoma (diagnosis, etiology, prevention & control)
• Celecoxib
• Cyclooxygenase Inhibitors (administration & dosage, therapeutic use)
• Liposomes
• Mice
• Mice, Hairless
• Neoplasm Recurrence, Local
• Neoplasms, Radiation-Induced (diagnosis, etiology, prevention & control)
• Neoplasms, Squamous Cell (diagnosis, etiology, prevention & control)
• Pyrazoles (administration & dosage, therapeutic use)
• Radiation Dosage
• Skin (pathology, radiation effects)
• Skin Neoplasms (diagnosis, etiology, prevention & control)
• Sulfonamides (administration & dosage, therapeutic use)
• Time Factors
• Tocopherols (administration & dosage, chemistry, therapeutic use)
• Treatment Outcome
• Ultraviolet Rays (adverse effects)