Anti-metastasis effect of fucoidan from Undaria pinnatifida sporophylls in mouse hepatocarcinoma Hca-F cells.

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

doi:10.1371/journal.pone.0106071

Peisheng Wang, Zhichao Liu + Show 6 more

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https://doi.org/10.1371/journal.pone.0106071

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Journal: PloS one	Publication Date: Aug 27, 2014
Citations: 45	License type: CC BY 4.0

Affiliation: Dalian Medical University, Liaoning Normal University

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.

Highlights

Tumor metastasis is a multistep process by which cancer cells from the primary tumor enter the vasculature and circulate, migrate, and invade to distant secondary organs or tissues
Matrix metalloproteinases (MMPs) and their specific inhibitors–tissue inhibitor of metalloproteinases (TIMPs) have been acknowledged as major critical molecules associated with extracellular matrix (ECM) degradation and cancer cell invasion during metastasis [3,4,5,6]
After Ups-fucoidan withdrawal, counting the death cell by trypan blue staining and calculating the cell death rate (D%), and all the D% in each concentrations group of Upsfucoidan is not statistically significant compared with control

Summary

Introduction

Tumor metastasis is a multistep process by which cancer cells from the primary tumor enter the vasculature and circulate, migrate, and invade to distant secondary organs or tissues. The processes of the tumor metastatic cascade require the survival, growth, invasion, and signal transduction potential of tumor cells. Cyclin D1 and cyclin-dependent kinase 4 (CDK4) are key players in the cell cycle and growth [1]. Matrix metalloproteinases (MMPs) and their specific inhibitors–tissue inhibitor of metalloproteinases (TIMPs) have been acknowledged as major critical molecules associated with extracellular matrix (ECM) degradation and cancer cell invasion during metastasis [3,4,5,6]. Some researchers have reported that the proliferative actions of VEGF require activation of both the extracellular signal–regulated kinase (ERK) and Akt signaling cascades [8,9,10]

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