Anti-tumor and anti-angiogenic effects of Fucoidan on prostate cancer: possible JAK-STAT3 pathway.

Abstract

BACKGROUND:

Prostate cancer is the most common cancer in men in the United States. Fucoidan is a bioactive polysaccharide extracted mainly from algae. The aim of this study was to investigate anti-tumor and anti-angiogenic effects of fucoidan in both cell-based assays and mouse xenograft model, as well as to clarify possible role of JAK-STAT3 pathway in the protection.

METHODS:

DU-145 human prostate cancer cells were treated with 100-1000 μg/mL of fucoidan. Cell viability, proliferation, migration and tube formation were studied using MTT, EdU, Transwell and Matrigel assays, respectively. Athymic nude mice were subcutaneously injected with DU-145 cells to induce xenograft model, and treated by oral gavage with 20 mg/kg of fucoidan for 28 days. Tumor volume and weight were recorded. Vascular density in tumor tissue was determined by hemoglobin assay and endothelium biomarker analysis. Protein expression and phosphorylation of JAK and STAT3 were determined by Western blot. Activation of gene promoters was investigated by chromatin Immunoprecipitation.

RESULTS:

Fucoidan could dose-dependently inhibit cell viability and proliferation of DU-145 cells. Besides, fucoidan also inhibited cell migration in Transwell and tube formation in Matrigel. In animal study, 28-day treatment of fucoidan significantly hindered the tumor growth and inhibited angiogenesis, with decreased hemoglobin content and reduced mRNA expression of CD31 and CD105 in tumor tissue. Furthermore, phosphorylated JAK and STAT3 in tumor tissue were both reduced after fucoidan treatment, and promoter activation of STAT3-regulated genes, such as VEGF, Bcl-xL and Cyclin D1, was also significantly reduced after treatment.

CONCLUSIONS:

All these findings provided novel complementary and alternative strategies to treat prostate cancer.

• Authors: Xin Rui, Hua-Feng Pan, Si-Liang Shao, Xiao-Ming Xu
• Journal: BMC complementary and alternative medicine (BMC Complement Altern Med) Vol. 17 Issue 1 Pg. 378 (Aug 01 2017) ISSN: 1472-6882 [Electronic] England
• PMID: 28764703 (Publication Type: Journal Article)

Chemical References

• Angiogenesis Inhibitors
• Antineoplastic Agents
• Biological Products
• Polysaccharides
• STAT3 Transcription Factor
• fucoidan
• Janus Kinases

Topics

• Angiogenesis Inhibitors (pharmacology, therapeutic use)
• Animals
• Antineoplastic Agents (pharmacology, therapeutic use)
• Biological Products (pharmacology, therapeutic use)
• Cell Line, Tumor
• Cell Movement
• Cell Proliferation
• Cell Survival
• Humans
• Janus Kinases (metabolism)
• Male
• Mice
• Mice, Nude
• Phaeophyceae (chemistry)
• Polysaccharides (pharmacology, therapeutic use)
• Promoter Regions, Genetic
• Prostatic Neoplasms (drug therapy, metabolism)
• STAT3 Transcription Factor (metabolism)
• Xenograft Model Antitumor Assays