PMID- 24310794
OWN - NLM
STAT- MEDLINE
DCOM- 20140807
LR  - 20240109
IS  - 1757-9708 (Electronic)
IS  - 1757-9694 (Linking)
VI  - 6
IP  - 1
DP  - 2014 Jan
TI  - Identification of pro- and anti-proliferative oligosaccharides of heparins.
PG  - 90-9
LID - 10.1039/c3ib40206a [doi]
AB  - Heparins, unfractionated heparin (UFH) and low molecular weight heparins (LMWHs), 
      are heterogeneous mixtures of anticoagulant and non-anticoagulant 
      oligosaccharides. In addition to their well-known anticoagulant effect, heparins 
      have shown to mediate a wide range of non-anticoagulant effects, including the 
      modulation of cellular growth. However, contradictory results have been reported 
      with regard to their effects on cellular proliferation, with some studies 
      suggesting anti-proliferative while others indicating pro-proliferative effects. 
      This study investigated the proliferation of human colonic epithelial cancer 
      cells in the presence of UFH and LMWHs (enoxaparin and dalteparin). In our 
      experimental setting, all heparins caused a dose-dependent reduction in cellular 
      growth, which correlated well with the induction of cell cycle arrest in the G(1) 
      phase and which was not associated with significant changes in cell viability. 
      The effects on cellular proliferation of 14 different oligosaccharides of 
      enoxaparin obtained through ion-exchange chromatography were also assessed. 
      Surprisingly, only two oligosaccharides showed distinctive anti-proliferative 
      effects while the majority of oligosaccharides actually stimulated proliferation. 
      Interestingly, the smallest oligosaccharide devoid of any anticoagulant activity 
      showed the strongest anti-proliferative effect. Notably, heparins are currently 
      standardised only according to their anticoagulant activity but not based on 
      other non-anticoagulant properties. Our results indicate that slight differences 
      in the composition of heparins' non-anticoagulant oligosaccharides, due to 
      different origins of material and preparation methods, have the potential to 
      cause diverse effects and highlight the need for additional characterisation of 
      non-anticoagulant activities.
FAU - Lean, Qi Ying
AU  - Lean QY
AD  - School of Pharmacy, University of Tasmania, Hobart, TAS, Australia. 
      nguven@utas.edu.au.
FAU - Patel, Rahul P
AU  - Patel RP
FAU - Stewart, Niall
AU  - Stewart N
FAU - Sohal, Sukhwinder Singh
AU  - Sohal SS
FAU - Gueven, Nuri
AU  - Gueven N
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Integr Biol (Camb)
JT  - Integrative biology : quantitative biosciences from nano to macro
JID - 101478378
RN  - 0 (Enoxaparin)
RN  - 0 (Oligosaccharides)
RN  - S79O08V79F (Dalteparin)
SB  - IM
MH  - Cell Count
MH  - Cell Cycle Checkpoints/*physiology
MH  - Cell Proliferation/*drug effects
MH  - Cell Survival/physiology
MH  - Chromatography, Ion Exchange/methods
MH  - Dalteparin/*chemistry/pharmacology
MH  - Enoxaparin/*chemistry/pharmacology
MH  - Flow Cytometry
MH  - HCT116 Cells
MH  - HT29 Cells
MH  - Humans
MH  - Oligosaccharides/*chemistry/pharmacology
EDAT- 2013/12/07 06:00
MHDA- 2014/08/08 06:00
CRDT- 2013/12/07 06:00
PHST- 2013/12/07 06:00 [entrez]
PHST- 2013/12/07 06:00 [pubmed]
PHST- 2014/08/08 06:00 [medline]
AID - 10.1039/c3ib40206a [doi]
PST - ppublish
SO  - Integr Biol (Camb). 2014 Jan;6(1):90-9. doi: 10.1039/c3ib40206a.