Abstract

A novel protein-bound polysaccharide, CFPS-1, isolated from Corbicula fluminea, is composed predominantly of mannose (Man) and glucose (Glc) in a molar ratio of 3.1:12.7. The polysaccharide, with an average molecular weight of about 283 kDa, also contains 10.8% protein. Atomic force microscopy, high-performance liquid chromatography, Fourier transform infrared spectroscopy, gas chromatography/mass spectrometry, and nuclear magnetic resonance spectroscopy analyses revealed that CFPS-1 has a backbone of 1,6-linked and 1,4,6-linked-α-D-Glc, which is terminated with a 1-linked-α-D-Man residue at the O-4 position of 1,4,6-linked-α-D-Glc, in a molar ratio of 3:1:1. Preliminary in vitro bioactivity tests revealed that CFPS-1 effectively and dose-dependently inhibits human breast cancer MCF-7 and MDA-MB-231 cell growth, with an IC50 of 243 ± 6.79 and 1142 ± 14.84 μg/mL, respectively. In MCF-7, CFPS-1 produced a significant up-regulation of p53, p21, Bax and cleaved caspase-7 and down-regulation of Cdk4, cyclin D1, Bcl-2 and caspase-7. These effects resulted in cell cycle blockade at the S-phase and apoptosis induction. In contrast, in MDA-MB-231, with limited degree of change in cell cycle distribution, CFPS-1 increases the proportion of cells in apoptotic sub-G1 phase executed by down-regulation of Bcl-2 and caspase-7 and up-regulation of Bax and cleaved caspase-7. This study extends our understanding of the anticancer mechanism of C. fluminea protein-bound polysaccharide.

Highlights

  • The freshwater clam Corbicula fluminea is a popular edible bivalve mollusk in Asia

  • The purified CFPS-1 isolated from C. fluminea was a white powder, with a yield of 0.93% of the dry material after lyophilization

  • The high-performance size exclusion chromatography profile of CFPS-1 showed as a single peak, corresponding to a mean molecular weight (Mw) of 283 kDa [2]

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Summary

Introduction

The freshwater clam Corbicula fluminea is a popular edible bivalve mollusk in Asia. It has been important in the human diet since ancient times in China because of its delicious taste and nutritional value [1]. We previously reported that a C. fluminea sulfate polysaccharide, CFPS2, displays marked inhibitory effects on the growth of SKOV3 human ovarian carcinoma cells and SGC7901 human gastric cancer cells [2]. Zhu et al reported that another bioactive. Corbicula fluminea Proteoglycan Inhibits MCF-7 and MDA-MB-231 Human Breast Cancer Cells. Science and Technology Special Projects of Zhejiang, China 2013C03045-1) and Zhejiang Provincial Program for the Cultivation of High-level Innovative Health Talents, http://www.decmin.com/ zj_view.asp?id=919. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

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