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-na&#xef;ve dogs with intermediate or large cell multicentric LSA. Lymph node cell aspirates were obtained before and after 7&#x2009;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&#x2009;<&#x2009;.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.