Anti-cancer and analgesic effects of resolvin D2 in oral squamous cell carcinoma. (1st September 2018)

• Record Type: Journal Article
• Authors: Ye, Yi; Scheff, Nicole N.; Bernabé, Daniel; Salvo, Elizabeth; Ono, Kentaro; Liu, Cheng; Veeramachaneni, Ratna; Viet, Chi T.; Viet, Dan T.; Dolan, John C.; Schmidt, Brian L.
• Is Part Of: Neuropharmacology. Volume 139(2018)
• Page Start: 182
• Page End: 193
• Publication Date: 2018-09-01
• Subjects: Oral cancer -- Squamous cell carcinoma -- Pain -- Inflammation -- Resolvin; Neuropsychopharmacology -- Periodicals; Autonomic Agents -- Periodicals; Neuropsychopharmacologie -- Périodiques; Neuropsychopharmacology; Periodicals; Electronic journals; 615.78
• DOI: 10.1016/j.neuropharm.2018.07.016
• Languages: English
• ISSNs: 0028-3908

Abstract

Abstract: Oral cancer is often painful and lethal. Oral cancer progression and pain may result from shared pathways that involve unresolved inflammation and elevated levels of pro-inflammatory cytokines. Resolvin D-series (RvDs) are endogenous lipid mediators derived from omega-3 fatty acids that exhibit pro-resolution and anti-inflammatory actions. These mediators have recently emerged as a novel class of therapeutics for diseases that involve inflammation; the specific roles of RvDs in oral cancer and associated pain are not defined. The present study investigated the potential of RvDs (RvD1 and RvD2) to treat oral cancer and alleviate oral cancer pain. We found down-regulated mRNA levels of GPR18 and GPR32 (which code for receptors RvD1 and RvD2) in oral cancer cells. Both RvD1 and RvD2 inhibited oral cancer proliferation in vitro . Using two validated mouse oral squamous cell carcinoma xenograft models, we found that RvD2, the more potent anti-inflammatory lipid mediator, significantly reduced tumor size. The mechanism of this action might involve suppression of IL-6, C-X-C motif chemokine 10 (CXCL10), and reduction of tumor necrosis. RvD2 generated short-lasting analgesia in xenograft cancer models, which coincided with decreased neutrophil infiltration and myeloperoxidase activity. Using a cancer supernatant model, we demonstrated that RvD2 reduced cancer-derived cytokines/chemokines (TNF-α, IL-6, CXCL10, and MCP-1), cancer mediator-induced CD11b + Ly6G − myeloid cells, and nociception. We infer from our results that manipulation of the endogenous pro-resolution pathway might provide a novel approach to improve oral cancer and cancer pain treatment. Highlights: RvD2 inhibits oral squamous cell carcinoma growth. RvD2 counter-regulates cancer-derived cytokine/chemokines IL-6 and CXCL10. RvD2 transiently inhibits mechanical and thermal pain and immune cell infiltration. RvD2 might enhance endogenous clearance of tumor necrosis. RvD1 exhibits long-lasting attenuation of thermal pain.