[alpha]-TEA & celecoxib in skin cancer prevention & therapy

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Date

2005-05-21

Authors

Best, Shelley Rae

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Abstract

The cyclooxygenase-2 (COX-2) specific inhibitor celecoxib reduces tumor incidence in skin cancer and progression of skin tumors, but the benefits of celecoxib are lost with cessation of treatment. The absence of lasting effects highlights the need for an effective combination treatment. In this study we investigate the efficacy of combinations of [alpha]-TEA, a novel vitamin E analog, and celecoxib in preventing UVB induced skin cancer. SKH-1 hairless mice were irradiated 3 times/week with 90 mJ/cm² and this dose was increased by 10% weekly to a maximum of 175 mJ/cm². UV was stopped at 24 weeks, at which time there were an average of 5.8 papillomas/mouse. The mice were then placed in one of four treatment groups: no treatment, [alpha]-TEA, celecoxib, or combination treatment. The control group continued to produce new tumors in a linear manner such that by week 28, tumor number nearly doubled. The group receiving [alpha]- TEA was marginally effective and reduced tumor number by 36% by week 28. Both celecoxib and combination treatment groups were significantly different than control, showing a 59% and a 62% reduction in tumor reduction, respectively. To determine whether tumor regression was permanent or required continued treatment, all treatments were stopped at 28 weeks. Over the next 3 weeks, tumor recurrence was not significant in the [alpha]-TEA alone group. A significant number of tumors reappeared in the celecoxib alone group. The combination treatment group that was removed from treatment showed an increase in average tumor number per mouse, but this increase was less substantial than the increase observed in the celecoxib alone group. It is concluded that [alpha]-TEA is an effective therapeutic agent for skin cancer, and the benefits of treatment of [alpha]-TEA are lasting

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