Fucoidan is a fucose-containing sulfated polysaccharide derived from brown seaweeds, crude extracts of which are commercially available as nutritional supplements. Recent studies have demonstrated antiproliferative, antiangiogenic, and anticancer properties of fucoidan in vitro. Accordingly, the anticancer effects of fucoidan have been shown to vary depending on its structure, while it can target multiple receptors or signaling molecules in various cell types, including tumor cells and immune cells. Low toxicity and the in vitro effects of fucoidan mentioned above make it a suitable agent for cancer prevention or treatment. However, preclinical development of natural marine products requires in vivo examination of purified compounds in animal tumor models. This review discusses the effects of systemic and local administration of fucoidan on tumor growth, angiogenesis, and immune reaction and whether in vivo and in vitro results are likely applicable to the development of fucoidan as a marine anticancer drug.

Many marine triterpene glycosides have in vitro and in vivo activities with very low toxicity, suggesting that they are suitable agents for the prevention and treatment of different diseases, particularly cancer. However, the molecular mechanisms of action of natural marine compounds in cancer, immune, and other various cells are not fully known. This review focuses on the structural characteristics of marine triterpene glycosides and how these affect their biological activities and molecular mechanisms. In particular, the membranotropic and membranolytic activities of frondoside A and cucumariosides from sea cucumbers and their ability to induce cytotoxicity and apoptosis have been discussed, with a focus on structure-activity relationships. In addition, the structural characteristics and antitumor effects of stichoposide C and stichoposide D have been reviewed along with underlying their molecular mechanisms.

BACKGROUND: An increase in the level of the vascular endothelial growth factor (VEGF) production has been reported in the peritoneal fluid (PF) of endometriosis patients. This suggests that changes in the vascular permeability and angiogenesis play an important role in the pathophysiology of this disease. This study examined the effects of the PF obtained from endometriosis patients on the release of VEGF by neutrophils and monocytes. METHODS: Neutrophils and monocytes were obtained from young healthy volunteers and cultured with the PF obtained from either endometriosis patients (EPF) (n = 18) or a control group (CPF) (n = 4). A human monocyte/macrophage cell line, THP-1, was cultured with either 10% EPF or 10% CPF. The PF and culture supernatants were assayed for VEGF using ELISA. Real-time PCR and Western blotting were used to measure the VEGF mRNA and protein expression level, respectively. RESULTS: The VEGF levels were higher in the EPF than in the CPF (591 ± 75 versus 185 ± 31 pg/ml, P < 0.05). However, the level of VEGF released by THP-1 cells in CPF and EPF was similar. The EPF induced the release of VEGF by neutrophils, but no VEGF was released by monocytes. The VEGF mRNA expression levels in the neutrophils were higher in the EPF, which was abrogated by cycloheximide, suggesting that the EPF induces the production of VEGF in neutrophils. Neutralizing antibodies against IL-8 and TNF-α did not completely prevent the EPF-induced release of VEGF by the neutrophils, even though these growth factors stimulated the release of VEGF by neutrophils. There was a positive correlation between the VEGF and IL-10 concentrations in the EPF (correlation coefficient = 0.549, P = 0.012, n = 18), but the neutralizing antibody of IL-10 did not affect the release of VEGF by the EPF-treated neutrophils. CONCLUSION: The EPF induced the production and release of VEGF by neutrophils, suggesting that neutrophils may be a source of peritoneal VEGF. In addition, neutrophil-derived VEGF might be a marker for diagnosing endometriosis.

We show that epigallocatechin‐3 gallate (EGCG), a major component of green tea, stimulates phospholipase D (PLD) activity in U87 human astroglioma cells. EGCG‐induced PLD activation was abolished by the phospholipase C (PLC) inhibitor and a lipase inactive PLC‐γ1 mutant, which is dependent on intracellular or extracellular Ca²⁺, with the possible involvement of Ca²⁺/calmodulin‐dependent protein kinase II (CaM kinase II). EGCG induced translocation of PLC‐γ1 from the cytosol to the membrane and PLC‐γ1 interaction with PLD1. EGCG regulates the activity of PLD by modulating the redox state of the cells, and antioxidants reverse this effect. Moreover, EGCG‐induced PLD activation was reduced by PKC inhibitors or down‐regulation of PKC. Taken together, these results show that, in human astroglioma cells, EGCG regulates PLD activity via a signaling pathway involving changes in the redox state that stimulates a PLC‐γ1 [Ins(1,4,5)P₃‐Ca²⁺]–CaM kinase II–PLD pathway and a PLC‐γ1 (diacylglycerol)–PKC–PLD pathway.

An artificial three-dimensional (3D) culture system that mimics the tumor microenvironment in vitro is an essential tool for investigating the cross-talk between immune and cancer cells in tumors. In this study, we developed a 3D culture system using an electrospun poly(ε-caprolactone) (PCL) nanofibrous scaffold (NFS). A hybrid NFS containing an uninterrupted network of nano- and submicron-scale fibers (400 nm to 2 µm) was generated by deposition onto a stainless steel mesh instead of an aluminum plate. The hybrid NFS contained multiplanar pores in a 3D structure. Surface-seeded mouse CT26 colon cancer cells and bone marrow-derived dendritic cells (BM-DCs) were able to infiltrate the hybrid NFS within several hours. BM-DCs cultured on PCL nanofibers showed a baseline inactive form, and lipopolysaccharide (LPS)-activated BM-DCs showed increased expression of CD86 and major histocompatibility complex Class II. Actin and phosphorylated FAK were enriched where unstimulated and LPS-stimulated BM-DCs contacted the fibers in the 3D hybrid NFS. When BM-DCs were cocultured with mitoxantrone-treated CT26 cells in a 3D hybrid NFS, BM-DCs sprouted cytoplasm to, migrated to, synapsed with, and engulfed mitoxantrone-treated CT26 cancer cells, which were similar to the naturally occurring cross-talk between these two types of cells. The 3D hybrid NFS developed here provides a 3D structure for coculture of cancer and immune cells.

Chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII) plays an essential role in angiogenesis and development. A previous study showed that the expression of COUP-TFII enhanced invasiveness of human lung carcinoma cells. However, no published data are available concerning the biological and clinical significance of COUP-TFII expression in colorectal cancer. Thus, our objective was to explore the expression of COUP-TFII in colorectal cancer as well as its association with clinicopathological features, and to evaluate the role of COUP-TFII as a prognostic indicator in colorectal cancer. We investigated the presence of COUP-TFII in human colorectal cancer tissues and adjacent normal tissues from 95 primary colorectal cancer patients by immunohistochemistry. The correlation between the expression of COUP-TFII and clinicopathologic features was investigated. The 3-year disease-free survival (DFS) and overall survival (OS) of patients with tumors expressing different levels of COUP-TFII were evaluated by the Kaplan-Meier method. No significant correlation was found between COUP-TFII expression and age at surgery, gender, histopathologic differentiation, vessel invasion, carcinoembryonic antigen (CEA), or nodal involvement. However, survival analysis showed that the COUP-TFII-positive group had a significantly better OS compared to COUP-TFII-negative group (80.4% vs. 57.7%, P=0.0491). Based on our results, COUP-TFII may represent a biomarker for good prognosis in colorectal cancer.