resolvin-d1 and Neoplasms

Epithelial mesenchymal transition (EMT) is a biological process that plays a critical role in cancer progression. Blocking the process of EMT can be an essential strategy in the development of anticancer drugs. In this paper, we briefly introduce recent research trends and issues of EMT, focusing on the relationship of EMT with the entire cycle of inflammation (from initiation to resolution of inflammation). Recent findings on the relationship between EMT and immune evasion are discussed. We will also explore the importance of controlling inflammation by anti-inflammatory compounds and specialized pro-resolving lipids to inhibit EMT process in cancer.

Topics: Animals; Anti-Inflammatory Agents; Docosahexaenoic Acids; Epithelial-Mesenchymal Transition; Humans; Lipids; Neoplasms; Tumor Microenvironment

Omega-3 fatty acids (omega3-FA) were shown to attenuate growth and induce apoptosis in a variety of human cancer cell lines derived from colonic, pancreatic, prostate, and breast cancer. In addition, recent findings indicate that omega3-FA act synergistically with chemotherapeutic agents and may also be used to enhance tumour radiosensitivity. The mechanisms underlying the anti-tumour effects of omega3-FA are complex. Incorporation of omega3-FA in biological membranes alters the profile of lipid mediators generated during inflammatory reactions. Furthermore, omega3-FA act as ligands of nuclear peroxisome proliferator-activated receptors that attenuate transcription of NF-kappaB-dependent genes. Thereby, the cyclooxygenase-2/prostaglandin E(2)-dependent production of pro-angiogenic vascular endothelial growth factor and levels of anti-apoptotic bcl-2 and bcl-X(L) are decreased. Eicosanoid-independent pro-apoptotic pathways include enhanced lipid peroxidation, modulation of mitochondrial calcium homeostasis and enhanced production of reactive oxygen species as well as activation of p53. This review article will give a comprehensive overview over the pleiotropic actions of omega3-FA and will discuss the potential of omega3-FA and derivatives like conjugated eicosapentaenoic acid as important nutritional adjuvant therapeutics in the management of various human cancer diseases and the impact of nutritional omega-3 FA on cancer prevention.

Topics: Antineoplastic Agents; Apoptosis; Cell Line, Tumor; Cyclooxygenase 2; Dietary Fats; Dinoprostone; Docosahexaenoic Acids; Fatty Acids, Omega-3; Female; Humans; Lipoxins; Male; Neoplasms; Peroxisome Proliferator-Activated Receptors; Tumor Suppressor Protein p53

Innovative therapies to target tumor-associated neutrophils (PMN) are of clinical interest, since these cells are centrally involved in cancer inflammation and tumor progression. Resolvin D1 (RvD1) is a lipid autacoid that promotes resolution of inflammation by regulating the activity of distinct immune and non-immune cells. Here, using human papilloma virus (HPV) tumorigenesis as a model, we investigated whether RvD1 modulates PMN to reduce tumor progression.. Growth-curve assays with multiple cell lines and in vivo grafting of two distinct HPV-positive cells in syngeneic mice were used to determine if RvD1 reduced cancer growth. To investigate if and how RvD1 modulates PMN activities, RNA sequencing and multiplex cytokine ELISA of human PMN in co-culture with HPV-positive cells, coupled with pharmacological depletion of PMN in vivo, were performed. The mouse intratumoral immune cell composition was evaluated through FACS analysis. Growth-curve assays and in vivo pharmacological depletion were used to evaluate anti-tumor activities of human and mouse monocytes, respectively. Bioinformatic analysis of The Cancer Genome Atlas (TCGA) database was exploited to validate experimental findings in patients.. RvD1 decreased in vitro and in vivo proliferation of human and mouse HPV-positive cancer cells through stimulation of PMN anti-tumor activities. In addition, RvD1 stimulated a PMN-dependent recruitment of classical monocytes as key determinant to reduce tumor growth in vivo. In human in vitro systems, exposure of PMN to RvD1 increased the production of the monocyte chemoattractant protein-1 (MCP-1), and enhanced transmigration of classical monocytes, with potent anti-tumor actions, toward HPV-positive cancer cells. Consistently, mining of immune cells infiltration levels in cervical cancer patients from the TCGA database evidenced an enhanced immune reaction and better clinical outcomes in patients with higher intratumoral monocytes as compared to patients with higher PMN infiltration.. RvD1 reduces cancer growth by activating PMN anti-cancer activities and encouraging a protective PMN-dependent recruitment of anti-tumor monocytes. These findings demonstrate efficacy of RvD1 as an innovative therapeutic able to stimulate PMN reprogramming to an anti-cancer phenotype that restrains tumor growth.

Topics: Animals; Docosahexaenoic Acids; Humans; Mice; Monocytes; Neoplasms; Neutrophils

Topics: Animals; Antineoplastic Agents; Aspirin; Chemokine CCL2; Chemokines; Cytokines; Disease Models, Animal; Docosahexaenoic Acids; Eicosanoids; Fatty Acids, Unsaturated; Female; Inflammation; Lipoxins; Macrophages; Metabolomics; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Microtubule-Associated Proteins; Neoplasm Metastasis; Neoplasms; Nerve Tissue Proteins; Phagocytosis; Plasminogen Inactivators; Prostaglandins