Anti-Metastasis Effect of Fucoidan from Undaria pinnatifida Sporophylls in Mouse Hepatocarcinoma Hca-F Cells

Abstract

Metastasis is one of the major causes of cancer-related death. It is a complex biological process involving multiple genes, steps, and phases. It is also closely connected to many biological activities of cancer cells, such as growth, invasion, adhesion, hematogenous metastasis, and lymphatic metastasis. Fucoidan derived from Undaria pinnatifida sporophylls (Ups-fucoidan) is a sulfated polysaccharide with more biological activities than other fucoidans. However, there is no information on the effects of Ups-fucoidan on tumor invasion and metastasis. We used the mouse hepatocarcinoma Hca-F cell line, which has high invasive and lymphatic metastasis potential in vitro and in vivo, to examine the effect of Ups-fucoidan on cancer cell invasion and metastasis. Ups-fucoidan exerted a concentration- and time-dependent inhibitory effect on tumor metastasis in vivo and inhibited Hca-F cell growth, migration, invasion, and adhesion capabilities in vitro. Ups-fucoidan inhibited growth and metastasis by downregulating vascular endothelial growth factor (VEGF) C/VEGF receptor 3, hepatocyte growth factor/c-MET, cyclin D1, cyclin-dependent kinase 4, phosphorylated (p) phosphoinositide 3-kinase, p-Akt, p-extracellular signal regulated kinase (ERK) 1/2, and nuclear transcription factor-κB (NF-κB), and suppressed adhesion and invasion by downregulating L-Selectin, and upregulating protein levels of tissue inhibitor of metalloproteinases (TIMPs). The results suggest that Ups-fucoidan suppresses Hca-F cell growth, adhesion, invasion, and metastasis capabilities and that these functions are mediated through the mechanism involving inactivation of the NF-κB pathway mediated by PI3K/Akt and ERK signaling pathways.

Fucoidan Inhibition of Osteosarcoma Cells is Species and Molecular Weight Dependent

“…Other fucoidans have also been reported to affect cell cycle in a similar way. Fucoidan from U. pinnatifida (commercially available or laboratory prepared) targeted p21Cip1/Waf and E2F-1 in PC-3 cells [38] and cyclin D1 and CDK4 in mouse hepatoma Hca-F cells [49]. In line with these studies, we showed that both crude fucoidans investigated led to cell cycle arrest in the G1 phase of cell cycle.…”

A map describing the association between effective components of traditional Chinese medicine and signaling pathways in cancer cells in vitro and in vivo

“…Meanwhile, fucoidan reduces tumor size in LLC1-xenograft male C57BL/6 mice (109). In mouse hepatocarcinoma Hca-F cells, fucoidan can suppress tumor cell growth, adhesion, invasion, and metastasis through the NF-κB pathway and ERK pathway in vitro and in vivo (110). In 4T1 mouse breast cancer cells, fucoidan was proved to inhibit cancer cell growth by blockage of the Wnt/β-catenin signaling pathway in vitro and in vivo (111).…”

Fucoidan Induces ROS‐Dependent Apoptosis in 5637 Human Bladder Cancer Cells by Downregulating Telomerase Activity via Inactivation of the PI3K/Akt Signaling Pathway

“…Fucoidan is a naturally occurring sulfated polysaccharide compound isolated from marine brown algae [Kusaykin et al, 2008;Fitton and Stringer, 2015] that has a wide variety of biological activities, including anti-viral, anti-bacterial, anti-oxidant, anti-inflammatory, and immunomodulatory activities, and to promote stem cell differentiation [Park et al, 2011;Fitton and Stringer, 2015;Kim et al, 2015]. Fucoidan can suppress the proliferation of diverse types of cancer cell lines and inhibit metastasis and angiogenesis [Senthilkumar and Kim, 2014;Wang et al, 2014;Chen et al, 2015;Huang et al, 2015]. In previous studies, we demonstrated that the anti-cancer activity of fucoidan is mediated through cell cycle arrest at the G1 phase, induction of caspase-dependent apoptosis in human bladder cancer cells [Park et al, 2014], and activation of p38 mitogen-activated protein kinase (MAPK) in human leukemic cells [Park et al, 2013].…”