Concomitant Inhibition of FASN and SREBP Provides a Promising Therapy for CTCL.

Cutaneous T cell lymphoma (CTCL) is a group of non-Hodgkin's primary cutaneous T cell lymphomas, with Mycosis Fungoides and Sézary syndrome (SS) being the two most common subtypes. Fatty acid synthase (FASN) is a crucial enzyme that catalyses the biosynthesis of fatty acids, which has been reported to play an oncogenic role in various malignancies but not in CTCL so far. Herein, we show that FASN is highly expressed in CTCL cell lines and in peripheral blood mononuclear cells (PBMCs) from CTCL patients, while it is not in PBMCs from healthy individuals. The inhibition of FASN in CTCL cell lines impairs cell viability, survival, and proliferation, but, interestingly, it also increases FASN expression. However, inhibiting sterol regulatory element binding protein (SREBP), a transcription factor that promotes the expression of FASN, partially reversed the upregulation of FASN induced by FASN inhibitors. Thus, the combination of FASN and SREBP inhibitors enhanced the effects on both CTCL cell lines and PBMCs from SS patients, where a valid inhibition on cell proliferation could be verified. Importantly, compared to non-malignant cells, primary malignant cells are more sensitive to the inhibition of FASN and SREBP, making the combination of FASN and SREBP inhibitors a promising novel therapeutic strategy in CTCL.

Salt Taste Enhancing l-Arginyl Dipeptides from Casein and Lysozyme Released by Peptidases of Basidiomycota.

Some l-arginyl dipeptides were recently identified as salt taste enhancers, thus opening the possibility to reduce dietary sodium uptake without compromising palatability. A screening of 15 basidiomycete fungi resulted in the identification of 5 species secreting a high peptidolytic activity (>3 kAU/mL; azocasein assay). PFP-LC-MS/MS and HILIC-MS/MS confirmed that l-arginyl dipeptides were liberated when casein or lysozyme served as substrate. Much higher yields of dipeptides (42-75 µmol/g substrate) were released from lysozyme than from casein. The lysozyme hydrolysate generated by the complex set of peptidases of Trametes versicolor showed the highest l-arginyl dipeptide yields and a significant salt taste enhancing effect in a model cheese matrix and in a curd cheese. With a broad spectrum of novel specific and nonspecific peptidases active in the slightly acidic pH range, T. versicolor might be a suitable enzyme source for low-salt dairy products.