Docosahexaenoic acid inhibits both NLRP3 inflammasome assembly and JNK-mediated mature IL-1β secretion in 5-fluorouracil-treated MDSC: implication in cancer treatment.

ABSTRACT: Limitation of 5-fluorouracil (5-FU) anticancer efficacy is due to IL-1β secretion by myeloid-derived suppressor cells (MDSC), according to a previous pre-clinical report. Release of mature IL-1β is a consequence of 5-FU-mediated NLRP3 activation and subsequent caspase-1 activity in MDSC. IL-1β sustains tumor growth recovery in 5-FU-treated mice. Docosahexaenoic acid (DHA) belongs to omega-3 fatty acid family and harbors both anticancer and anti-inflammatory properties, which could improve 5-FU chemotherapy. Here, we demonstrate that DHA inhibits 5-FU-induced IL-1β secretion and caspase-1 activity in a MDSC cell line (MSC-2). Accordingly, we showed that DHA-enriched diet reduces circulating IL-1β concentration and tumor recurrence in 5-FU-treated tumor-bearing mice. Treatment with 5-FU led

SUBMITTER: Dumont A 

PROVIDER: S-EPMC6584690 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature