Journal
PLOS ONE
Volume 11, Issue 12, Pages -Publisher
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0167889
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Funding
- National Natural Science Foundation of China [31371872]
- Public Projects of Zhejiang Province [2015C32017]
- Program of Health and Medicine Science in Zhejiang Province [2015RCA003]
- Major Science and Technology Special Projects of Zhejiang, China [2013C03045-1]
- Zhejiang Provincial Program for the Cultivation of High-level Innovative Health Talents
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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-alpha-D-Glc, which is terminated with a 1-linked-alpha-D-Man residue at the O-4 position of 1,4,6-linked-alpha-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 MCF7 and MDA-MB-231 cell growth, with an IC50 of 243 +/- 6.79 and 1142 +/- 14.84 mu g/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.
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