C6 Ceramide (d18:1/6:0) as a Novel Treatment of Cutaneous T Cell Lymphoma

SIMPLE SUMMARY: There is no curative treatment for mycosis fungoides and Sézary syndrome, which are the most frequent forms of cutaneous T cell lymphoma (CTCL). Short-chain ceramides like C6 Ceramide are known to induce cell death by both apoptosis and necrosis. Here, we demonstrate that C6 Ceramide strongly reduced cell viability and induced cell death in CTCL cell lines but not in HaCaT keratinocytes and primary human keratinocytes. C6 Ceramide was rapidly metabolized by both keratinocyte cell types but not by CTCL cells. These results provide the basis for further clinical trials with topical applicated C6 Ceramide against mycosis fungoides and Sézary syndrome. ABSTRACT: Cutaneous T cell lymphomas (CTCLs) represent a heterogeneous group of T cell lymphomas that primarily affect the skin. The most frequent forms of CTCL are mycosis fungoides and Sézary syndrome. Both are characterized by frequent recurrence, developing chronic conditions and high mortality with a lack of a curative treatment. In this study, we evaluated the effect of short-chain, cell-permeable C6 Ceramide (C6Cer) on CTCL cell lines and keratinocytes. C6Cer significantly reduced cell viability of CTCL cell lines and induced cell death via apoptosis and necrosis. In contrast, primary human keratinocytes and HaCaT keratinocytes were less affected by C6Cer. Both keratinocyte cell lines showed higher expressions of ceramide catabolizing enzymes and HaCaT keratinocytes were able to metabolize C6Cer faster and more efficiently than CTCL cell lines, which might explain the observed protective effects. Along with other existing skin-directed therapies, C6Cer could be a novel well-tolerated drug for the topical treatment of CTCL.