15-hydroxyeicosatrienoic acid (15-HETrE) suppresses epidermal hyperproliferation via the modulation of nuclear transcription factor (AP-1) and apoptosis.
The purpose of this study was to ascertain whether the antiproliferative effect of 15-hydroxyeicosatrienoic acid (15-HETrE), a monohydroxy fatty acid generated from dihomo-gamma-linolenic acid, in an experimentally induced guinea pig hyperproliferative model involves alterations in nuclear transcription factor (AP-1) and apoptosis. The topical application of docosahexaenoic acid (DHA) to normal guinea pig skin elicited a severe hyperplasia which was accompanied by the suppression of AP-1 expression in a time-dependent manner. Since apoptosis is pivotal in tissue turnover, the expression of two apoptotic proteins (Bcl-2 and caspase-3) after DHA and 15-HETrE treatment was explored. DHA-induced hyperproliferation enhanced the expression of Bcl-2 (an antiapoptotic protein) but inhibited the expression of caspase-3 (an apoptotic protein). 15-HETrE, on the other hand, reversed the DHA-induced epidermal hyperplasia, and upregulated epidermal AP-1 expression. These events paralleled the suppression of Bcl-2 and the elevation of caspase-3. Taken together, these results suggest that the antiproliferative effect of 15-HETrE may, at least in part, be via the modulation of AP-1 and apoptosis.
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Department of Dermatology, School of Medicine, University of California at Davis, 95616, USA.
Pham
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Ziboh
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D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D004281:Docosahexaenoic Acids / Q000494:pharmacology; D004338:Drug Combinations; D000078404:Epidermal Cells; D004817:Epidermis / Q000378:metabolism; D006168:Guinea Pigs; D006893:Hydroxyeicosatetraenoic Acids / Q000494:pharmacology*; D006965:Hyperplasia; D008297:Male; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012867:Skin / Q000187:drug effects / Q000473:pathology; D013997:Time Factors; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors / Q000378:metabolism*
D004338:Drug Combinations; D006893:Hydroxyeicosatetraenoic Acids; D019253:Proto-Oncogene Proteins c-bcl-2; D018808:Transcription Factor AP-1; D004281:Docosahexaenoic Acids; C095123:15-hydroxyeicosatrienoic acid; D053148:Caspase 3; D020169:Caspases