ABSTRACT
Cancer-related inflammation (CRI) is associated with the malignant progression of several cancer types. Targeting these pathways is a novel promising strategy for cancer prevention and treatment. In this present study, we evaluated the efficacy of ?-l-guluronic acid (ALG), a potent anti-inflammatory agent on breast cancer-related inflammation both in vitro and in vivo conditions. Our results indicated that ALG can effectively inhibit the CRI and tumor-promoting mediators (COX-2, MMP2, MMP9, VEGF and proinflammatory cytokines) without direct toxic effects on the cells. Moreover, it was found that, ALG can effectively inhibit the tumor cell adhesion to extracellular matrix, seeding in implantation tissue, reduce accumulation of immunosuppressive and inflammatory cells in tumor-bearing mice. These findings were associated with decreased tumor growth, metastasis, angiogenesis and prolonged mice survival. In conclusion, our data provide a cellular and molecular justification for the use of nonsteroidal anti-inflammatory drugs (NSAIDs) in treating cancer and imply the potential anti-tumor activity of ALG therapy via inhibition of CRI. These findings could lead to the establishment of novel NSAID-based cancer therapy in the near future and open a new horizon for cancer treatment.
Subject(s)
Anti-Inflammatory Agents/therapeutic use , Antineoplastic Agents/therapeutic use , Hexuronic Acids/therapeutic use , Inflammation/complications , Inflammation/drug therapy , Mammary Neoplasms, Animal/complications , Mammary Neoplasms, Animal/drug therapy , Animals , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Cell Adhesion , Cell Line, Tumor , Cell Proliferation/drug effects , Cyclooxygenase 2/metabolism , Cytokines/metabolism , Disease Models, Animal , Female , Hexuronic Acids/chemistry , Hexuronic Acids/pharmacology , Immunosuppression Therapy , Inflammation/pathology , Mammary Neoplasms, Animal/enzymology , Mammary Neoplasms, Animal/pathology , Matrix Metalloproteinase 2/metabolism , Matrix Metalloproteinase 9/metabolism , Mice, Inbred BALB C , Neoplasm Metastasis , Survival Analysis , Tumor MicroenvironmentABSTRACT
INTRODUCTION: Inflammatory bowel diseases (IBD) are immune-mediated disorders that result from an aberrant immunological response to the gut luminal antigen in genetically susceptible patients. IBD is categorized into two serotype, Crohn's diseases (CD) and ulcerative colitis (UC), both subtype are important cause of gastrointestinal diseases. The increasing rate of hospitalization, with the high economic burden experienced by the IBD patients, calls for more concerted research efforts to design a potent and affordable treatment option for the treatment of IBD. AIMS/OBJECTIVE: This research was designed to test the efficacy and potency of ß-D Mannuronic acid (M2000) and assess if it could serve as a better therapeutic option in the treatment of IBD. METHODOLOGY: Ten (10)ml of blood was aseptically collected into an EDTA container, from 24 IBD patients and 24 normal healthy controls. PBMC was isolated and stimulated with 1µg/ml of LPS in cell culture plate and incubated for 4h. The cells were later treated with 10µg/ml and 50µg/ml of ß-D Mannuronic acid (M2000) and incubated for 24h at 37°C under 5% CO2 and 100% humidity. The RNA extractions, cDNA synthesis, and QRT-PCR were performed. RESULTS: Our findings showed a significant down-regulation of TNF-α and IL-17 gene expression, while the expression of FOXP3 gene was significantly up-regulated. CONCLUSION: This result has indicated that ß-D Mannuronic acid (M2000) have immunoregulatory and anti-inflammatory effects on these cytokines that are pivotal in the pathogenesis of IBD.
