Anti‐inflammatory and anti‐tumor effects of α-l-guluronic acid (G2013) on cancer-related inflammation in a murine breast cancer model

• Published in: Biomedicine & pharmacotherapy 2018-02, Vol.98, p.793-800
• Main Authors: Hosseini, Fatemeh, Mahdian-Shakib, Ahmad, Jadidi-Niaragh, Farhad, Enderami, Seyed Ehsan, Mohammadi, Hamed, Hemmatzadeh, Maryam, Mohammed, Hussaini Alhassan, Anissian, Ali, Kokhaei, Parviz, Mirshafiey, Abbas, Hassannia, Hadi
• Format: Article
• Language: English
• Subjects: Animals; Anti-Inflammatory Agents - chemistry; Anti-Inflammatory Agents - pharmacology; Anti-Inflammatory Agents - therapeutic use; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Breast cancer; Cancer-related inflammation; Cell Adhesion; Cell Line, Tumor; Cell Proliferation - drug effects; Cyclooxygenase 2 - metabolism; Cytokines - metabolism; Disease Models, Animal; Female; Guluronic acid; Hexuronic Acids - chemistry; Hexuronic Acids - pharmacology; Hexuronic Acids - therapeutic use; Immunosuppression; Inflammation - complications; Inflammation - drug therapy; Inflammation - pathology; Mammary Neoplasms, Animal - complications; Mammary Neoplasms, Animal - drug therapy; Mammary Neoplasms, Animal - enzymology; Mammary Neoplasms, Animal - pathology; Matrix Metalloproteinase 2 - metabolism; Matrix Metalloproteinase 9 - metabolism; Medicin och hälsovetenskap; Mice, Inbred BALB C; Neoplasm Metastasis; NSAIDs; Survival Analysis; Tumor Microenvironment
• ISSN: 0753-3322; 1950-6007; 1950-6007
• DOI: 10.1016/j.biopha.2017.12.111

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 α-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.