In this blog post, I will be sharing the study conducted by Guang Yang et al. on “Antitumor activity of fucoidan against diffuse large B cell lymphoma in vitro and in vivo“. The study includes the key findings from their research.
B-cell lymphoma, known as DLBCL, is a form of cancer that specifically targets B cells, a particular type of blood cell. Among B-cell cancers, a particular subgroup is constituted by B cells with enlarged nuclei that proliferate and invade the tissue diffusely, resulting in intermediate-grade malignant tumors with a rapid disease progression within a few months. Due to the circulation of B cells in both blood vessels and lymph vessels, DLBCL has the potential to manifest in multiple organs within the body. Although commonly observed in the lymph nodes, approximately 40% of patients experience the disease in locations other than the lymph nodes. In addition to lymph nodes, the gastrointestinal tract, including the stomach, as well as the bones, mediastinum (between the left and right lungs), testicles, the central nervous system (such as the brain and spinal cord), and the skin are frequently affected sites.
Combination chemo-immunotherapy improves the overall survival of patients with DLBCL, but over 30% of these patients develop relapsed or refractory disease.
In addition, fucoidan has been observed to have diverse biological activities, such as antibacterial, antiviral, anti-inflammatory, antiangiogenic, and antioxidant effects. The attention on the anticancer effects of fucoidan has been increasing, especially in recent times. Significantly, a clinical trial combining both phase I and phase II in human subjects demonstrated the low toxicity of fucoidan.
The main objective of this study was to investigate the effectiveness of fucoidan extracted from Fucus vesiculosus in inhibiting the growth of diffuse large B-cell lymphoma (DLBCL) cells. The evaluation of its anticancer activity was conducted through both in vitro and in vivo experiments.
First, to investigate the effect of fucoidan on the proliferation and survival of DLBCL cells, different concentrations of fucoidan were used to test six DLBCL cell lines (GC subtypes OCI-LY8, SUDHL-4, and DB, TMD8, U2932, and NU-DUL-1, ABC subtype) for 48 hours. CCK8 assay showed that fucoidan inhibited the proliferation of DLBCL cells in a dose-dependent manner. (See Figure. 1A) The IC50 values for these cell lines were 82.3 (OCI-LY8), 95.5 (DB), 80.0 (SUDHL-4), 97.5 (TMD8), 101.6 (U2932), and 93.7 μg/ml (NU-DUL-1). The effect of fucoidan on DLBCL cells was also time-dependent.
The regulation of cell cycle progression and cell death plays a crucial role in the efficacy of antitumor drugs. G0/G1 phase arrest was induced in OCI-LY8 cells following treatment with Fucoidan, and comparable results were observed in SUDHL-4 and NU-DUL-1 cell lines.
Fucoidan inhibited the proliferation of DLBCL cells in a dose- and time-dependent manner and fucoidan treatment caused G0/G1 cell cycle arrest, which included upregulation of p21 and downregulation of cyclin D1, Cdk4, and Cdk6. Fucoidan also induced caspase-dependent cell apoptosis in DLBCL cell lines and primary DLBCL cells. (See Figure. 2A) Fucoidan treatment resulted in the decline of mitochondrial membrane potential and the release of cytochrome c and apoptosis-inducing factors from the mitochondria into the cytosol. (Figure. 2D)
The use of combination chemotherapy as the initial treatment for DLBCL is widely accepted and considered to be the standard approach. The administration of R-CHOP (rituximab-cyclophosphamide, doxorubicin, vincristine, prednisone) therapy has been shown to enhance complete response rates and extend event-free and overall survival in geriatric patients with DLBCL. As a result, a thorough investigation was conducted to determine if the combination of fucoidan and these drugs could potentially improve the effectiveness of anti-DLBCL treatment. It is important to mention that no synergistic effect was detected with this combination.
In this study, the researchers proceeded to examine the effect of CFZ (Carfilzomib). CFZ (Carfilzomib) was enhanced by fucoidan in DLBCL cell lines and primary DLBCL cells but showed little cytotoxicity to normal CD34+ cells. Fucoidan also enhanced the activity of carfilzomib in killing DLBCL cells. The oral administration of fucoidan successfully suppressed tumor growth in a xenograft mouse model. Thus, the study findings revealed a novel function of fucoidan as an anti-DLBCL agent that can be used in the clinical treatment of DLBCL.
Source: Acta Biochimica et Biophysica Sinica, Volume 47, Issue 11: 925 – 931 (2015)