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AuthorCecchi, Marta
AuthorPaccosi, Sara
AuthorSilvano, Angela
AuthorEid, Ali Hussein
AuthorParenti, Astrid
Available date2023-09-06T15:29:26Z
Publication Date2021-01-01
Publication NamePharmaceuticals
Identifierhttp://dx.doi.org/10.3390/ph14030211
CitationCecchi, M., Paccosi, S., Silvano, A., Eid, A. H., & Parenti, A. (2021). Dexamethasone induces the expression and function of tryptophan-2-3-dioxygenase in sk-mel-28 melanoma cells. Pharmaceuticals, 14(3), 211.‏
URIhttps://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85102861895&origin=inward
URIhttp://hdl.handle.net/10576/47310
AbstractTryptophan-2,3-dioxygenase (TDO) is one of the key tryptophan-catabolizing enzymes with immunoregulatory properties in cancer. Contrary to expectation, clinical trials showed that inhibitors of the ubiquitously expressed enzyme, indoleamine-2,3-dioxygenase-1 (IDO1), do not provide benefits in melanoma patients. This prompted the hypothesis that TDO may be a more attractive target. Because the promoter of TDO harbors glucocorticoid response elements (GREs), we aimed to assess whether dexamethasone (dex), a commonly used glucocorticoid, modulates TDO expression by means of RT-PCR and immunofluorescence and function by assessing cell proliferation and migration as well as metalloproteinase activity. Our results show that, in SK-Mel-28 melanoma cells, dex up-regulated TDO and its downstream effector aryl hydrocarbon receptor (AHR) but not IDO1. Furthermore, dex stimulated cellular proliferation and migration and poten-tiated MMP2 activity. These effects were inhibited by the selective TDO inhibitor 680C91 and enhanced by IDO1 inhibitors. Taken together, our results demonstrate that the metastatic melanoma cell line SK-Mel-28 possesses a functional TDO which can also modulate cancer cell phenotype di-rectly rather than through immune suppression. Thus, TDO appears to be a promising, tractable target in the management or the treatment of melanoma progression.
Languageen
PublisherMDPI
Subject680C91
Dexamethasone
Epacadostat
Indoleamine-2,3-dioxygenase-1
Melanoma
Migration
MMP2
Proliferation
SK-Mel-28
Tryptophan-2,3-dioxygenase
TitleDexamethasone induces the expression and function of tryptophan-2-3-dioxygenase in sk-mel-28 melanoma cells
TypeArticle
Issue Number3
Volume Number14
dc.accessType Open Access


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