Prospective evaluation of the lymph node proteome in dogs with multicentric lymphoma supplemented with sulforaphane

Abstract

Background: Lymphoma (LSA) is a common malignancy in dogs. Epigenetic changes are linked to LSA pathogenesis and poor prognosis in humans, and LSA pathogenesis in dogs. Sulforaphane (SFN), an epigenetic-targeting compound, has recently gained interest in relation to cancer prevention and therapy. Objective: Examine the impact of oral supplementation with SFN on the lymph node proteome of dogs with multicentric LSA. Animals: Seven client-owned dogs with multicentric LSA. Methods: Prospective, nonrandomized, noncontrolled study in treatment-naïve dogs with intermediate or large cell multicentric LSA. Lymph node cell aspirates were obtained before and after 7 days of oral supplementation with SFN, and analyzed via label-free mass spectrometry, immunoblots, and Gene Set Enrichment Analysis. Results: There was no clinical response and no adverse events attributed to SFN. For individual dogs, the expression of up to 650 proteins changed by at least 2-fold (range, 2-100) after supplementation with SFN. When all dogs where analyzed together, 14 proteins were significantly downregulated, and 10 proteins were significantly upregulated after supplementation with SFN (P < .05). Proteins and gene sets impacted by SFN were commonly involved in immunity, response to oxidative stress, gene transcription, apoptosis, protein transport, maturation and ubiquitination. Conclusions and Clinical Importance: Sulforaphane is associated with major changes in the proteome of neoplastic lymphocytes in dogs.

Epigenetic Alterations in Canine Malignant Lymphoma: Future and Clinical Outcomes

“…Regarding deacetylation drugs, a multicentric study in canine lymphoma shows that treatment with sulforaphane, an isothiocyanate derived from some vegetables, is associated with change in proteome [136], although its results in clinical practice are as yet unknown. However, the effect of sulforaphane as an HDAC and DNMT inhibitor has been proven in human cancer prostate cells [137], acute lymphoblastic leukaemia cells [138] and multiple myeloma [139].…”