Abstract: Objective To evaluate the anticoagulant and antineoplastic activities of chemically modified low-molecular-weight
heparin (LMWH). Methods LMWH obtained by splitting unfractionated heparin (UFH) with sodium periodate oxidation and
sodium borohydride reduction was subjected to acetylation catalyzed by DCC and DMAP to produce acetylated LMWH
(ALMWH). The anticoagulant activity of ALMWH was determined in mice, and its antiproliferative and anti-invasion
activities was assessed in human breast cancer cells MDA-MB-231 and MFC-7. Results The anticoagulant activity of LMWH
was decreased significantly after acetylation. The concentrations of commercial LMWH* and ALMWH for doubling the
coagulation time (CT) were 33.04 μmol/L and 223.56 μmol/L, respectively, and the IC50 of ALMWH for doubling CT was 6
times of that of LMWH*. ALMWH and LMWH at 0.1, 0.3, 0.9, 2.7 and 8.1 mmol/L both significantly inhibited the proliferation
of MDA-MB-231 and MCF-7 cells in a concentration-dependent manner, but ALMWH produced stronger inhibitory effects.
The IC50 of LMWH and ALMWH for inhibiting cell proliferation was 3168.4 μmol/L and 152.6 μmol/L in MCF-7 cells, and
12299.6 μmol/L and 22.2 μmol/L in MDA-MB-231 cells, respectively. ALMWH and LMWH all markedly suppressed the
invasion of MDA-MB-231 cells with comparable effects. Conclusion Chemical modification of structure can endow LMWH
with a low anticoagulant and high antiproliferative activities.