Psoralen binding and inhibition of epidermal growth factor binding by psoralen/ultraviolet light (PUVA) in human epithelial cells.
The psoralen analogs 8-methoxypsoralen (8-MOP) and 4,5',8-trimethylpsoralen (TMP), in combination with ultraviolet light (UVA, 320-400 nm), are potent modulators of epidermal cell growth and differentiation and are commonly used in photochemotherapy of psoriasis and vitiligo. We have used KB cells, a human epithelial cell line, to examine the mechanism of action of these compounds. In KB cells, 8-MOP was found to bind to specific, saturable receptor sites. Binding of [3H]-8-MOP to its receptor was inhibited by TMP as well as psoralen. We found that binding of these analogs to the cells followed by UVA light treatment was associated with inhibition of epidermal growth factor (EGF) receptor binding. Inhibition of EGF binding was temperature dependent, occurred immediately following UVA light exposure, and appeared to be due to a decrease in the number of EGF receptors. In KB cells, 125I-labeled EGF surface receptor binding is followed by its rapid internalization and degradation. We found that photoactivated psoralens also inhibited internalization of 125I-EGF, but had no apparent effect on EGF metabolism. These data indicate that the cell surface membrane may be an important target for the photoactivated psoralens. In addition, since photoactivated psoralens regulate cell proliferation, the interaction of these compounds with EGF receptor function may underlie their biological activity.
Laskin
J D
JD
Department of Environmental and Community Medicine, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway 08854.
Lee
E
E
D001667:Binding, Competitive; D002460:Cell Line / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000378:metabolism*; D066246:ErbB Receptors / Q000187:drug effects; D006801:Humans; D008730:Methoxsalen / Q000494:pharmacology*; D011701:PUVA Therapy; D011956:Receptors, Cell Surface / Q000187:drug effects; D012878:Skin Neoplasms / Q000378:metabolism; D013696:Temperature; D014307:Trioxsalen / Q000494:pharmacology*
D011956:Receptors, Cell Surface; C052763:psoralen receptor; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D008730:Methoxsalen; D014307:Trioxsalen