Journal Article

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

Liu, Zhichao, Liu, Xianli, Zhang, Cuili, Hou, Lin, Teng, Hongming, Zou, Xiangyang, Wang, Peisheng

2014

Overview

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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: 1-Phosphatidylinositol 3-kinase / Adhesion / AKT protein / Angiogenesis / Animals / Anticoagulants / Antineoplastic Agents, Phytogenic - isolation & purification / Antineoplastic Agents, Phytogenic - pharmacology / Apoptosis / Biological activity / Biology and Life Sciences / Biotechnology / Brain cancer / Breast cancer / c-Met protein / Cancer / Cancer metastasis / Carcinoma, Hepatocellular - drug therapy / Carcinoma, Hepatocellular - genetics / Carcinoma, Hepatocellular - metabolism / Carcinoma, Hepatocellular - pathology / Cell adhesion & migration / Cell Adhesion - drug effects / Cell cycle / Cell death / Cell growth / Cell Line, Tumor / Cell migration / Cell Movement - drug effects / Cell Proliferation - drug effects / Chromatography / Cyclin D1 / Cyclin D1 - antagonists & inhibitors / Cyclin D1 - genetics / Cyclin D1 - metabolism / Cyclin-dependent kinase / Cyclin-dependent kinase 4 / Cyclin-Dependent Kinase 4 - antagonists & inhibitors / Cyclin-Dependent Kinase 4 - genetics / Cyclin-Dependent Kinase 4 - metabolism / Deactivation / Dose-Response Relationship, Drug / Extracellular signal-regulated kinase / Fucoidan / Gene Expression Regulation, Neoplastic / Health aspects / Hepatocyte growth factor / Hepatocyte Growth Factor - antagonists & inhibitors / Hepatocyte Growth Factor - genetics / Hepatocyte Growth Factor - metabolism / Inactivation / Inhibition / Invasiveness / Kinases / L-selectin / Liver cancer / Liver Neoplasms, Experimental - drug therapy / Liver Neoplasms, Experimental - genetics / Liver Neoplasms, Experimental - metabolism / Liver Neoplasms, Experimental - pathology / Lymphatic Metastasis / Lymphatic system / Male / MAP Kinase Signaling System / Medical research / Medicine and Health Sciences / Metastases / Metastasis / Mice / Molecular weight / NF-kappa B - antagonists & inhibitors / NF-kappa B - genetics / NF-kappa B - metabolism / NF-κB protein / Phosphatidylinositol 3-Kinases - genetics / Phosphatidylinositol 3-Kinases - metabolism / Phosphoinositide-3 Kinase Inhibitors / Physiology / Plant Extracts - chemistry / Polysaccharides - isolation & purification / Polysaccharides - pharmacology / Proto-Oncogene Proteins c-met - antagonists & inhibitors / Proto-Oncogene Proteins c-met - genetics / Proto-Oncogene Proteins c-met - metabolism / Receptors, Vascular Endothelial Growth Factor - antagonists & inhibitors / Receptors, Vascular Endothelial Growth Factor - genetics / Receptors, Vascular Endothelial Growth Factor - metabolism / Signal transduction / Signaling / Sulfates / Sulfuric acid / Tissue inhibitor of metalloproteinases / Undaria - chemistry / Undaria pinnatifida / Vascular endothelial growth factor / Vascular Endothelial Growth Factor A - antagonists & inhibitors / Vascular Endothelial Growth Factor A - genetics / Vascular Endothelial Growth Factor A - metabolism